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Mechanosensitive Piezo1 channel in physiology and pathophysiology of the central nervous system

AGEING RESEARCH REVIEWS (2023)

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Article Engineering, Biomedical

Mechanical strain in the mouse astrocytic lamina increases after exposure to recombinant trypsin

Arina Korneva et al.

Summary: Understanding the responses of astrocytes in the optic nerve head to mechanical and biochemical stimuli is crucial for studying retinal ganglion cell axon degeneration in glaucoma. In a mouse model, elevated intraocular pressure caused alterations in the junctions between astrocytic processes and the peripapillary sclera, leading to increased structural compliance of the optic nerve head. Experimental treatment with TrypLE enzyme partially reproduced these alterations, suggesting the significance of astrocyte-sclera junction separation in increasing ONH compliance.

ACTA BIOMATERIALIA (2023)

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Article Neurosciences

Mechanosensitive channel Piezo1 is an essential regulator in cell cycle progression of optic nerve head astrocytes

Yue Wan et al.

Summary: Optic nerve head (ONH) astrocytes play a crucial role in supporting neuronal axons through their mechanical sensitivity, mediated by the ion channel Piezo1. Knockdown or overexpression of Piezo1 in vitro revealed its necessity but insufficiency in ONH astrocyte proliferation. Loss of Piezo1 led to cell cycle arrest, possibly through decreased YAP nuclear localization and downregulation of cell cycle-associated factors. Gene ontology analysis highlighted the impact of Piezo1 on cell division processes. These findings establish Piezo1 as an essential regulator of cell cycle progression in ONH astrocytes.

GLIA (2023)

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Editorial Material Clinical Neurology

Multiple sclerosis progression: time for a new mechanism-driven framework

Tanja Kuhlmann et al.

Summary: Traditionally, multiple sclerosis has been categorized into distinct clinical descriptors, but accumulating evidence suggests that it should be considered as a continuum with varying pathophysiological processes. A shift from acute injury to inflammation and neurodegeneration contributes to the progressive course, along with decreased neural resilience due to aging. Understanding the key mechanisms and quantifying progressive pathology can have implications for clinical care, treatment targets, and regulatory decisions.

LANCET NEUROLOGY (2023)

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Article Chemistry, Multidisciplinary

Mechanobiological modulation of blood-brain barrier permeability by laser stimulation of endothelial-targeted nanoparticles

Xiaoqing Li et al.

Summary: We demonstrated that targeting endothelial glycoproteins leads to >10-fold higher targeting efficiency than targeting tight junctions. By excitation of tight junction protein (JAM-A)-targeted and endothelial (glycocalyx)-targeted AuNPs, we gained insight into the mechanism of blood-brain barrier permeability, which is critical for brain disease treatment.

NANOSCALE (2023)

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Review Pharmacology & Pharmacy

Role of monomeric amyloid-β in cognitive performance in Alzheimer's disease: Insights from clinical trials with secretase inhibitors and monoclonal antibodies

Bruno P. Imbimbo et al.

Summary: According to the beta-amyloid (A beta) hypothesis, brain A beta accumulation is the primary cause of cognitive deficit and dementia in Alzheimer's disease (AD). While many anti-A beta drugs have failed in clinical trials, recent studies have shown encouraging results for antibodies that clear amyloid plaques. These findings suggest that decreased levels of soluble monomeric A beta may be the main driver of AD, rather than the aggregated forms.

PHARMACOLOGICAL RESEARCH (2023)

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Article Biochemistry & Molecular Biology

Activation of goblet cell Piezo1 alleviates mucus barrier damage in mice exposed to WAS by inhibiting H3K9me3 modification

Yan Xu et al.

Summary: Recent studies have shown that intestinal mechanical signals can regulate mucus synthesis and secretion through Piezo1. This study aimed to investigate the molecular mechanisms by which Piezo1 on goblet cells regulates mucus barrier function through methylation modification. The results revealed that Piezo1 mediates mechanical stimulation to inhibit H3K9me3, thereby promoting mucin2 expression in goblet cells and regulating mucus barrier function.

CELL AND BIOSCIENCE (2023)

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Article Multidisciplinary Sciences

Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis

Xiang-Zhi Fang et al.

Summary: This study demonstrated the key role of Piezo1 in mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis. Inhibiting Piezo1 activity could attenuate ATP release and EMT process in lung epithelial cells, thus improving pulmonary fibrosis.

JOURNAL OF ADVANCED RESEARCH (2023)

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Article Engineering, Biomedical

Matrix stiffness regulates the tight junction phenotypes and local barrier properties in tricellular regions in an iPSC-derived BBB model

Li Yan et al.

Summary: The blood-brain barrier (BBB) responds to mechanical cues and changes in substrate stiffness. The compromised function of the BBB is associated with neurological disorders and altered brain stiffness. Understanding the effects of matrix stiffness on BBB permeability could lead to new treatments for BBB dysfunction-related diseases.

ACTA BIOMATERIALIA (2023)

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Review Chemistry, Multidisciplinary

Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease

John H. Viles

Summary: The accumulation of amyloid-beta peptides (Aβ) is crucial in Alzheimer's disease development. The interaction between various Aβ assemblies and lipid membranes or membrane receptors result in increased membrane permeability and cellular homeostasis disruption, which plays a key role in the pathology of Alzheimer's disease. Aβ can affect lipid membranes in multiple ways, including a carpeting effect, a detergent effect, and the formation of Aβ ion-channel pores. Recent advancements in imaging techniques have improved our understanding of Aβ-induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will guide the development of therapeutics targeting Aβ cytotoxicity.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023)

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Review Biochemistry & Molecular Biology

Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Marc Charabati et al.

Summary: Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system. Neuroimmune interactions play a key role in MS pathology and offer potential targets for therapy. This review explores risk factors, pathogenesis mechanisms, current therapies, and emerging technologies for addressing clinical needs.

CELL (2023)

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Article Biochemistry & Molecular Biology

The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation

Wenqiang Fan et al.

Summary: Most adult hippocampal neural stem cells (NSCs) remain quiescent, but the activity of the transcriptional co-activator Yap1 is enriched in active NSCs. Genetic deletion of Yap1 reduces the proportion of active NSCs, indicating its role in regulating the transition from quiescence to activation. Overexpression of a gain-of-function Yap1 mutant leads to cell cycle entry in NSCs and astrocytes, and dysregulated Yap1 activity represses neurogenesis and induces glioblastoma stem cell-like characteristics.

EMBO JOURNAL (2023)

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Review Medicine, General & Internal

Glioblastoma and Other Primary Brain Malignancies in Adults: A Review

Lauren R. Schaff et al.

Summary: Malignant primary brain tumors cause a significant number of deaths in the United States each year, with glioblastomas being the most common type. The symptoms of these tumors can include headaches, seizures, neurocognitive impairment, and focal neurologic deficits. Diagnosis and treatment depends on the tumor type, with surgery, chemotherapy, and radiation often being used.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2023)

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Editorial Material Neurosciences

Piezo1 activation by stretching of uterine myometrium supports pregnancy and prevents preterm labour

Rakesh Kumar Majhi et al.

JOURNAL OF PHYSIOLOGY-LONDON (2023)

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Review Clinical Neurology

Ageing and multiple sclerosis

Jennifer S. Graves et al.

Summary: The age of patients with multiple sclerosis has a significant impact on the clinical course of the disease. Young patients tend to have relapsing remitting disease, while those with later onset face a faster development of disability. Ageing in the immune system and CNS might explain the poor response to current therapies for progressive multiple sclerosis. Ageing is also associated with higher risks of side-effects from multiple sclerosis therapies. Understanding the role of ageing in patients with multiple sclerosis could be crucial in preventing non-relapse-related progression. Research on potential therapies targeting senescent cells and ageing processes might provide effective strategies for remyelination and neuroprotection.

LANCET NEUROLOGY (2023)

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Article Neurosciences

Peripheral sensory neurons and non-neuronal cells express functional Piezo1 channels

Seung Min Shin et al.

Summary: In this study, the expression of Piezo1 protein in both primary sensory neurons and non-neuronal cells of the rat peripheral nervous system was observed. It was found that Piezo1 was present in approximately 60% of dorsal root ganglia neurons, with higher levels in small- and medium-sized neurons. Piezo1 was also detected in glial cells surrounding the neurons, Schwann cells, Merkel cells, and melanocytes. Functional Piezo1 channels were observed in various cell types, and the activation of Piezo1 led to an increase in intracellular calcium concentration. Furthermore, nerve injury-induced painful neuropathy was associated with increased Piezo1 expression and activation in sensory neurons and glial cells.

MOLECULAR PAIN (2023)

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Article Multidisciplinary Sciences

Myelin dysfunction drives amyloid-β deposition in models of Alzheimer's disease

Constanze Depp et al.

Summary: The main risk factor for Alzheimer's disease (AD), the leading cause of dementia, is age, but the reasons for this are still poorly understood. In this study, researchers found that age-related structural defects of myelin lead to the formation of amyloid-beta (Aβ) plaques, a hallmark of AD. Improving the health of oligodendrocytes and the integrity of myelin could be a promising target for delaying and slowing the progression of AD.

NATURE (2023)

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Review Neurosciences

Roles and regulation of microglia activity in multiple sclerosis: insights from animal models

Felix Distefano-Gagne et al.

Summary: This article discusses the mechanisms through which microglia contribute to neuropathology and the molecular mechanisms that regulate their function in demyelinating conditions. Microglia, as resident macrophages of the CNS, play critical roles in inflammatory lesions and associated neural dysfunctions. They have both detrimental effects on myelin and beneficial effects on tissue repair, and recent advances have shed light on their underlying molecular effectors.

NATURE REVIEWS NEUROSCIENCE (2023)

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Article Clinical Neurology

Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990-2030

Jiahui Fan et al.

Summary: This study systematically analyzed the global burden of ischemic stroke (IS) and its risk factors from 1990 to 2019, and predicted the death number of IS for 2020-2030. The study identified smoking, high sodium diet, high blood pressure, high cholesterol, kidney dysfunction, high blood glucose, and high body mass index as major risk factors for IS.

NEUROLOGY (2023)

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Article Multidisciplinary Sciences

Mechanosensitive stem cell fate choice is instructed by dynamic fluctuations in activation of Rho GTPases

Rocio G. Sampayo et al.

Summary: During the process of cell differentiation into tissues, cells are influenced by mechanical signals from the extracellular matrix (ECM), which regulate their fate. The activation of Rho GTPases plays a key role in sensing these cues, but the regulation and integration of the activation dynamics is still unclear. This study found that ECM stiffness cues not only alter the magnitude but also the temporal frequency of RhoA and Cdc42 activation in adult neural stem cells (NSCs). Further experiments using optogenetics showed that the frequency of RhoA and Cdc42 activation drives astrocytic versus neuronal differentiation, highlighting the functional significance of these dynamics.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Article Multidisciplinary Sciences

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Jiejun Zhu et al.

Summary: Transcranial low-intensity ultrasound is a promising noninvasive neuromodulation method. This study focuses on the biological mechanism of ultrasonic neuromodulation by studying the Piezo1-mediated effects. The results demonstrate that Piezo1 plays an important role in ultrasound-induced neuronal responses and limb movement.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Article Neurosciences

Inflammation condition sensitizes Piezo1 mechanosensitive channel in mouse cerebellum astrocyte

Donggyeom Yu et al.

Summary: This study found that LPS treatment increased Piezo1 currents, calcium influx, and cell migration velocity in neuroinflammatory astrocytes. These findings suggest that Piezo1 channel in astrocytes is a determinant of neuroinflammation pathogenesis, and further research may help in treating various neuronal diseases and inflammation caused by neuronal cell injury.

FRONTIERS IN CELLULAR NEUROSCIENCE (2023)

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Article Biotechnology & Applied Microbiology

Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke

Yiyang Li et al.

Summary: This study compared the protective efficacy of bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and brain endothelial cells derived extracellular vesicles (BEC-EVs) on blood-brain barrier (BBB) integrity after acute ischemic stroke (IS). The findings indicated that both types of EVs had similar protective effects on reducing cerebral infarction volume, BBB leakage, and enhancing the expression of tight junction proteins ZO-1 and Claudin-5. Furthermore, BMSC-EVs showed superior efficacy in suppressing Caveolin-1 and improving neurological function.

JOURNAL OF NANOBIOTECHNOLOGY (2023)

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Article Biotechnology & Applied Microbiology

Combination therapy with ultrasound and 2D nanomaterials promotes recovery after spinal cord injury via Piezo1 downregulation

Feng Zhang et al.

Summary: This study evaluated the combined effects of layered double hydroxide-coupled NT3 (MgFe-LDH/NT3) nanoparticles (NPs) and ultrasound (US) for spinal cord injury (SCI) therapy. The combined treatment promoted neural stem cell (NSC) differentiation into neurons and exerted anti-inflammatory effects in vitro. In a completely transected murine thoracic SCI model, the combined therapy improved behavioral and electrophysiological performance at eight weeks. RNA sequencing revealed that ultrasonic-induced Piezo1 downregulation is the core mechanism by which combined therapy promotes neurogenesis and inhibits inflammation.

JOURNAL OF NANOBIOTECHNOLOGY (2023)

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Article Engineering, Biomedical

Dynamic changes in mechanical properties of the adult rat spinal cord after injury

Chen Jin et al.

Summary: Spinal cord injury (SCI) is a debilitating condition with no cure, but regenerative medicine holds promise. This study characterized the mechanical properties of injured rat spinal cord tissue at different time points after crush injury. The results showed that the injured tissues had lower stiffness and higher viscosity immediately after injury, but gradually returned to baseline values and eventually displayed increased viscoelastic properties. These findings have important implications for the development of biomaterials for SCI repair.

ACTA BIOMATERIALIA (2023)

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Review Cell Biology

The role of PIEZO ion channels in the musculoskeletal system

Alireza Savadipour et al.

Summary: PIEZO1 and PIEZO2 are highly expressed mechanosensitive channels with diverse functions in various tissues. They play important roles in musculoskeletal health, including maintenance of muscle and bone mass, sensing tendon stretch, and regulation of senescence and apoptosis. PIEZO2 is essential for pain and touch perception as well as proprioception. Alterations in PIEZO channel mechanosensitivity can significantly affect these functions. Therapeutic approaches focus on controlling PIEZO1 and/or PIEZO2 activity through inhibition or dietary control. Overall, these studies highlight the crucial role of PIEZO channels in musculoskeletal health and suggest promising avenues for therapeutic modulation.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2023)

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Article Rheumatology

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis

Siwen Chen et al.

Summary: The aim of this study was to identify the role of Piezo1-mediated mechanotransduction in entheseal pathological new bone formation and explore the underlying molecular mechanism. It was found that Piezo1 was aberrantly upregulated in ligaments and entheseal tissues from patients with ankylosing spondylitis (AS) and animal models. Pharmacological and genetic inhibition of Piezo1 attenuated while its activation promoted pathological new bone formation. Mechanistically, activation of CaMKII signalling was found essential for Piezo1-mediated mechanotransduction. Additionally, Piezo1 was upregulated by AS-associated inflammatory cytokines.

ANNALS OF THE RHEUMATIC DISEASES (2023)

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Article Chemistry, Multidisciplinary

Chemical Activation and Mechanical Sensitization of Piezo1 Enhance TRAIL-Mediated Apoptosis in Glioblastoma Cells

Samantha V. Knoblauch et al.

Summary: Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, has a mean survival of less than 15 months after standard treatment. Temozolomide (TMZ) is the current standard of care, but its effectiveness is hindered by DNA repair and mutations in the p53 transcription factor. This study investigates the potential of activating Piezo1, a mechanoreceptor, to sensitize GBM cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment. The results show that combining Piezo1 activation with TRAIL significantly increases apoptosis in GBM cells and overcomes TMZ resistance.

ACS OMEGA (2023)

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Article Multidisciplinary Sciences

Matrix stiffness induces epithelial-to-mesenchymal transition via Piezo1-regulated calcium flux in prostate cancer cells

Maria Lopez-Cavestany et al.

Summary: Cells use calcium channels to sense changes in the extracellular space and convert them into intracellular signals. The current study explores how EMT is controlled in cancer cells by the mechanosensitive calcium channel Piezo1, which senses changes in extracellular matrix stiffness. By modeling the biophysical environment of healthy and cancerous prostate tissue, the study shows that increased matrix stiffness and activation of Piezo1 cause significant changes in calcium concentration, vimentin expression, aspect ratio, and E-cadherin expression. In conclusion, Piezo1-regulated calcium flux plays a role in prostate cancer cell metastasis by sensing changes in ECM stiffness and modulating EMT markers.

ISCIENCE (2023)

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Article Behavioral Sciences

New perspectives on the basal forebrain cholinergic system in Alzheimer's disease

Anne S. Berry et al.

Summary: The basal forebrain cholinergic system (BFCS) has been associated with age-related cognitive changes and Alzheimer's disease (AD). Despite limitations in cholinergic interventions, there is a renewed interest in studying the BFCS using novel frameworks. This article outlines the structure and function of the BFCS, its role in cognition and emotion, and its vulnerability to aging and AD. It also explores the BFCS in relation to the amyloid hypothesis, selective vulnerability, pathology spread, and sleep health in AD research.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2023)

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Article Multidisciplinary Sciences

Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes

Alireza Savadipour et al.

Summary: Through AFM and FEM studies, we found that PIEZO1 and PIEZO2 mediate calcium (Ca2+) signaling in chondrocytes at moderately high levels of cellular deformation, while at the highest strains, PIEZO1 functions independently of PIEZO2. Biophysical factors that increase apparent chondrocyte membrane tension also enhance PIEZO1-driven Ca2+ signaling. We identified a threshold of membrane stretch ratio that leads to PIEZO1-induced chondrocyte mechanical injury, suggesting potential targets for osteoarthritis prevention or treatment.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Article Clinical Neurology

Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation

Wen-Jun Su et al.

Summary: This study aims to elucidate the neuroimmune mechanism of diabetes-related depression. The activation of NLRP3 inflammasome, mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2023)

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Article Biochemistry & Molecular Biology

Oscillatory shear stress modulates Notch-mediated endothelial mesenchymal plasticity in cerebral arteriovenous malformations

C. L. Karthika et al.

Summary: This study reveals the association between disturbed blood flow and endothelial dysfunction in cerebral arteriovenous malformations (cAVMs). The authors found evidence of endothelial mesenchymal transition (EndMT) and activated Notch receptors in human cAVM nidus, as well as altered expression of cell adhesion markers. Furthermore, they demonstrate that oscillatory shear stress promotes the EndMT process and dysregulated expression of cell adhesion molecules, and this effect can be prevented by the small-molecule inhibitor RO4929097.

CELLULAR & MOLECULAR BIOLOGY LETTERS (2023)

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Review Pathology

The Immune Response in Multiple Sclerosis

Sofia Rodriguez Murua et al.

Summary: Multiple sclerosis is a chronic disease affecting the central nervous system, characterized by immune dysregulation and resulting in demyelination, neuronal damage, and degeneration. Genetic and environmental factors are believed to play a role in the onset and progression of this disease.

ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE (2022)

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Article Engineering, Biomedical

A paradigm shift: Bioengineering meets mechanobiology towards overcoming remyelination failure

Eva D. Carvalho et al.

Summary: Therapeutic strategies for central nervous system demyelinating diseases often fail due to a lack of understanding of the mechanisms of remyelination failure. The hostile environment surrounding a demyelination lesion inhibits myelin production and alters the mechanical properties of the tissue, leading to remyelination failure. The field of mechanobiology is being pointed out as a missing key to unravel the nature of (de)myelination. By exploring different models and using bioengineering approaches, new mechanobiology mechanisms and therapeutic targets can be identified, which can greatly impact the treatment of demyelinating diseases.

BIOMATERIALS (2022)

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Article Cell & Tissue Engineering

Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis

Yuhua Xie et al.

Summary: In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization leads to hair follicle stem cell (HFSC) loss through mechanical compression and apoptotic cell death. The mechanical compression activates the Piezo1 mechanosensitive channel, resulting in calcium influx and induction of ectopic apoptosis in HFSCs which are normally resistant to cell death. Continuous hair shaft miniaturization during aging and genetic hypotrichosis disorders causes long-term HFSC loss by inducing continuous ectopic apoptosis through Piezo1. These findings uncover the role of the inert hair shaft structure in governing HFSC survival and reveal a mechanosensory axis that regulates stem cell depletion induced by physical-niche-atrophy.

CELL STEM CELL (2022)

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Review Ophthalmology

Glaucoma and biomechanics

Babak N. Safa et al.

Summary: This review summarizes recent studies on the role of biomechanics in glaucoma. It is found that various tissues, including the trabecular meshwork, cornea, peripapillary sclera, optic nerve head/sheath, and iris, have biomechanical involvement in different forms of glaucoma. Multiple mechanosensory mechanisms and signaling pathways are identified in the trabecular meshwork and optic nerve head. Biomechanical information has also been incorporated into glaucoma prognoses. However, the understanding of the role of biomechanics in glaucoma is still incomplete.

CURRENT OPINION IN OPHTHALMOLOGY (2022)

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Article Ophthalmology

Piezo1 activation induces fibronectin reduction and PGF2α secretion via arachidonic acid cascade

Wataru Morozumi et al.

Summary: Glaucoma is a neurodegenerative disease that causes blindness, and reducing intraocular pressure (IOP) is crucial for its treatment. This study reveals that activating Piezo1 can lower IOP and suppress the accumulation of fibronectin. Activation of Piezo1 leads to increased expression of matrix metalloproteinase-2 (MMP-2) and cyclooxygenase (COX)-2, while decreasing the expression of fibronectin. Furthermore, Piezo1 activation promotes the arachidonic acid cascade, increasing the secretion of prostaglandin F2 alpha (PGF2 alpha) and the expression of MMP-2.

EXPERIMENTAL EYE RESEARCH (2022)

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Review Biochemistry & Molecular Biology

Glioma targeted therapy: insight into future of molecular approaches

Keyang Yang et al.

Summary: Gliomas are common brain tumors originating from glial cells. Treatment and prognosis differ significantly depending on the type of glioma. Traditional targeted therapy approaches have faced challenges, while new methods such as immunotherapy and the tumor microenvironment are gaining interest. More clinical trials are needed to evaluate the feasibility of personalized targeted therapy.

MOLECULAR CANCER (2022)

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Article Multidisciplinary Sciences

Single-cell dissection of the human brain vasculature

Francisco J. Garcia et al.

Summary: This study characterized the human cerebrovasculature at the single-cell level using experimental enrichment and sorting methods. The researchers identified specific expression patterns and markers for different cell types. They also studied changes in cerebrovascular cells from patients with Huntington's disease, revealing immune signaling activation and decreased blood-brain barrier integrity. Overall, this study provides a comprehensive molecular atlas of the human cerebrovasculature and has important implications for future research and therapy.

NATURE (2022)

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Review Clinical Neurology

The role of glial cells in multiple sclerosis disease progression

Luke M. Healy et al.

Summary: This Review discusses the involvement of astrocytes and microglia in the pathophysiology of progressive multiple sclerosis and considers current and future therapeutic approaches targeting glial cells. Greater understanding of the roles of these cells is needed to identify novel therapeutic opportunities for progressive MS.

NATURE REVIEWS NEUROLOGY (2022)

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Article Multidisciplinary Sciences

A single-cell atlas of the normal and malformed human brain vasculature

Ethan A. Winkler et al.

Summary: This study constructed a cell atlas of the adult human cerebrovasculature using transcriptomic data of cerebrovascular cells. The cellular and molecular perturbations in brain arteriovenous malformations were investigated, revealing abnormal vascular patterning and inflammation associated with the disease.

SCIENCE (2022)

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Article Cell Biology

PIEZO1 mediates a mechanothrombotic pathway in diabetes

Wandi Zhu et al.

Summary: This study identified dysregulation of the mechanosensory ion channel Piezo1 in platelets, red blood cells, and neutrophils of patients with type 2 diabetes mellitus (T2DM), leading to prothrombotic cellular responses. Inhibition of Piezo1 protected against thrombosis, providing a new target for modulating T2DM-related thrombosis.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Multidisciplinary Sciences

Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1

Weiyi Qian et al.

Summary: This study reveals defective mechano-phenotype signatures of vascular smooth muscle cells (VSMC) in abdominal aortic aneurysms (AAA), and identifies Piezo1 as a novel culprit of mechanically fatigued aorta in AAA.

NATURE COMMUNICATIONS (2022)

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Article Cell Biology

Piezo1 mediates endothelial atherogenic inflammatory responses via regulation of YAP/TAZ activation

Ying Yang et al.

Summary: The expression of Piezo1 is significantly increased in atherosclerotic mice and in vitro experiments induced by ox-LDL, and Piezo1 can mediate endothelial atherogenic inflammatory responses through the regulation of YAP/TAZ activation and nuclear localization. Piezo1 may be a potential therapeutic target for atherosclerotic diseases in the future.

HUMAN CELL (2022)

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Article Multidisciplinary Sciences

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Shaoyi Wang et al.

Summary: Excessive mechanical stress can induce ferroptosis in chondrocytes through Piezo1 activation and subsequent calcium influx, which might provide a potential target for osteoarthritis treatment.

JOURNAL OF ADVANCED RESEARCH (2022)

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Article Behavioral Sciences

Inhibition of Piezo1/Ca2+/calpain signaling in the rat basal forebrain reverses sleep deprivation-induced fear memory impairments

Tao Ma et al.

Summary: The study demonstrated that the Piezo1/Ca2+/calpain pathway in the basal forebrain modulates impaired fear conditioning caused by sleep deprivation. Activation or inhibition of Piezo1 protein can affect the cleavage of TrkB and fear memory in rats under sleep deprivation conditions.

BEHAVIOURAL BRAIN RESEARCH (2022)

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Article Biology

Fluid shear stress enhances T cell activation through Piezo1

Jacob M. Hope et al.

Summary: This study enhances the activation of T cells through mechanical means and finds that fluid shear stress treatment can increase the activation of signaling proteins and cytokine expression in T cells. These results reveal a new dynamic to T cell activation and suggest a potential pathophysiological relationship between T cell activation and fluid shear stress.

BMC BIOLOGY (2022)

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Article Oncology

Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling

Simei Zhang et al.

Summary: This study revealed that the abnormal expression of Piezo1 in melanoma accelerates the malignant progression by activating AKT/mTOR signaling. Knockdown of Piezo1 can inhibit the viability, migration, and invasion of melanoma cells. These findings suggest that Piezo1 may serve as a potential target for melanoma diagnosis and treatment.

CANCER BIOLOGY & THERAPY (2022)

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Article Cell Biology

Mechanosensitive Piezo1 channel in rat epididymal epithelial cells promotes transepithelial K+ secretion

Dong-Dong Gao et al.

Summary: The present study revealed the expression and function of Piezo1 channel in rat epididymal epithelium. Activation of Piezo1 channel promoted BK-mediated transepithelial K+ secretion, suggesting its important physiological role in the male reproductive tract.

CELL CALCIUM (2022)

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Article Cardiac & Cardiovascular Systems

Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions

Jessica Magid-Bernstein et al.

Summary: This review article provides an overview of the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of intracerebral hemorrhage (ICH). The incidence of hemorrhagic stroke has increased globally in the past 40 years, with changes in the cause over time due to improved hypertension management and increased use of anticoagulants. Preclinical and clinical trials have shed light on the underlying cause and mechanisms of injury from ICH, including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Although several trials have investigated the optimal medical and surgical management of ICH, there has been no clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management offers hope for reducing the devastating impact of this disease in the future.

CIRCULATION RESEARCH (2022)

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Article Cardiac & Cardiovascular Systems

Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries

Osama F. Harraz et al.

Summary: This study shows that Piezo1 channels act as mechanosensors in central nervous system capillaries, initiating crucial Ca2+ signals and having a profound impact on blood flow control.

CIRCULATION RESEARCH (2022)

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Review Neurosciences

Magnetic resonance elastography of the ageing brain in normal and demented populations: A systematic review

Ana Coelho et al.

Summary: Magnetic resonance elastography (MRE) can assess changes in brain mechanical properties during normal and pathological aging. Brain tissue stiffness decreases with aging and different brain regions exhibit varying effects on stiffness. Different dementia subtypes result in changes in brain stiffness.

HUMAN BRAIN MAPPING (2022)

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Article Peripheral Vascular Disease

Myeloid Piezo1 Deletion Protects Renal Fibrosis by Restraining Macrophage Infiltration and Activation

Yu He et al.

Summary: This study reveals the important role of Piezo1 in renal fibrosis, specifically in macrophages. The deletion of Piezo1 in macrophages can suppress macrophage inflammation, kidney fibrosis, and epithelial-mesenchymal transition. Targeting Piezo1 channels through genetic or pharmacological manipulations may be a promising approach for treating renal fibrosis.

HYPERTENSION (2022)

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Article Peripheral Vascular Disease

COMP (Cartilage Oligomeric Matrix Protein), a Novel PIEZO1 Regulator That Controls Blood Pressure

Hui Wang et al.

Summary: This study demonstrates that the matricellular protein COMP plays a protective role in blood pressure regulation by interacting with Piezo1, regulating intracellular calcium levels, eNOS activity, and nitric oxide production.

HYPERTENSION (2022)

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Article Biotechnology & Applied Microbiology

Self-amplifying loop of NF-κB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration

Jinna Wu et al.

Summary: Abnormal mechanical load is a significant risk factor for intervertebral disc degeneration (IDD) and cellular senescence plays a crucial role in this process. This study reveals the molecular mechanism underlying mechano-induced cellular senescence and IDD progression, highlighting the positive feedback loop between NF-kappa B and periostin. Additionally, neutralizing antibodies against periostin can interrupt this loop.

MOLECULAR THERAPY (2022)

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Article Multidisciplinary Sciences

Structure deformation and curvature sensing of PIEZO1 in lipid membranes

Xuzhong Yang et al.

Summary: This study reveals the structures and mechanisms of PIEZO1 channels in lipid membranes through observations of reconstituted PIEZO1 channels in liposome vesicles. It is found that PIEZO1 channels undergo substantial deformation in lipid membranes and the gating of the ion-conducting pathway is achieved through membrane tension-induced structural rearrangement. These findings provide important insights into the mechanosensitivity and curvature-based gating mechanism of PIEZO1 channels.

NATURE (2022)

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Article Cell Biology

The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance

Ryo Nakamichi et al.

Summary: This study reveals how mechanical stress affects physical performance by regulating PIEZO1 in tendons. The researchers found that tendon-specific knock-in mice with the gain-of-function variant R2482H Piezo1 had higher jumping abilities and faster running speeds due to enhanced tendon anabolism and increased expression of tendon-specific transcription factors. This finding suggests that PIEZO1 could be a potential target for enhancing physical performance.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Neurosciences

Mechanoreceptor Piezo1 Is Downregulated in Multiple Sclerosis Brain and Is Involved in the Maturation and Migration of Oligodendrocytes in vitro

Maria Velasco-Estevez et al.

Summary: In this study, the expression and role of the mechanoreceptor Piezo1 in oligodendrocytes and oligodendrocyte progenitor cells in the human brain were investigated. It was found that Piezo1 inhibition increased the proliferation and migration of MO3.13 oligodendrocytes, while activation of Piezo1 had opposite effects. Moreover, lower expression of Piezo1 was observed in the white matter of multiple sclerosis brains compared to healthy controls. This suggests that Piezo1-induced signaling may play an important role in the pathophysiology of multiple sclerosis.

FRONTIERS IN CELLULAR NEUROSCIENCE (2022)

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Article Biochemistry & Molecular Biology

Mechano-signaling via Piezo1 prevents activation and p53-mediated senescence of muscle stem cells

Yundong Peng et al.

Summary: Skeletal muscle stem cells, also known as satellite cells, play a crucial role in postnatal muscle growth and regeneration. This study reveals that Piezo1, a mechanosensitive ion channel, is essential for maintaining the quiescence and preventing senescence of muscle stem cells. Absence of Piezo1 leads to premature activation of these cells, impairs their proliferation and differentiation, and significantly hinders skeletal muscle regeneration. The inactivation of Piezo1 results in compensatory up-regulation of T-type voltage-gated Ca2+ channels, which increases the influx of Ca2+ and induces NOX4 expression through cPKC. The elevated expression of NOX4 in Piezo1-deficient cells leads to increased levels of reactive oxygen species (ROS) and DNA damage, causing P53-dependent cellular senescence and cell death. The study also highlights the importance of the P53/P21-axis in mediating the cellular defects caused by the absence of Piezo1. This research sheds light on the critical role of Piezo1-mediated mechano-signaling in maintaining the quiescence and preventing senescence of muscle stem cells, and suggests that reduced mechano-signaling during aging may contribute to the accumulation of senescent cells and the decline of muscle stem cell numbers in geriatric individuals.

REDOX BIOLOGY (2022)

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Article Neurosciences

Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses

Nina Choublier et al.

Summary: In this study, the response of human cerebral microvascular ECs to laminar physiological shear stress was investigated. The results showed that shear stress induced ECs quiescence and provided strong protection for hCMEC/D3 cells, suggesting a similar effect on the BBB. These findings provide new insights on the response of microvascular brain ECs to shear stress and the importance of shear stress for optimizing in vitro BBB models.

FLUIDS AND BARRIERS OF THE CNS (2022)

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Article Medicine, Research & Experimental

Piezo1 act as a potential oncogene in pancreatic cancer progression

Zeen Zhu et al.

Summary: Piezo1 plays an important role in the progression of pancreatic cancer, potentially serving as a promising target and oncogenic gene. It regulates the interaction between pancreatic cancer cells and the tumor microenvironment.

LIFE SCIENCES (2022)

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Article Cell Biology

Dendrites use mechanosensitive channels to proofread ligand-mediated neurite extension during morphogenesis

Li Tao et al.

Summary: This study reveals the importance of mechanosensitive channels in dendritic arborization, which activate local Ca2+ transients through the activation of voltage-gated Ca2+ channels. The mechanical activation of these channels relies on the anchoring of filopodia by dendrite ligand-receptor complexes.

DEVELOPMENTAL CELL (2022)

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Article Biochemistry & Molecular Biology

Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis

Xiaoqiang Yang et al.

Summary: The activation of Piezo1 can decrease the expression of renin in JG cells and mice, subsequently leading to a reduction in blood pressure, highlighting its therapeutic potential as a drug target of the renin-angiotensin system.

CELL AND BIOSCIENCE (2022)

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Article Biochemistry & Molecular Biology

Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone

Yan Zeng et al.

Summary: This study found that mechanical stress activates intracellular Ca2+ through Piezo1 channels, which regulates the opening of Cx43 hemichannels (HCs) mediated by PI3K-Akt signaling. The opened Cx43 HCs, together with other channels, sustain the intracellular Ca2+ signal, leading to bone anabolic function.

CELL AND BIOSCIENCE (2022)

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Article Physiology

The mechanosensitive Piezo1 channels contribute to the arterial medial calcification

Laszlo Szabo et al.

Summary: This study demonstrates the crucial role of Piezo1 channels in arterial medial calcification. The expression of Piezo1 is enhanced in calcified HAoSMCs, leading to an increased calcium influx upon stimulation. Inhibition of Piezo1 channels reduces calcification. These results reveal the pivotal role of Piezo1 channels in arterial medial calcification.

FRONTIERS IN PHYSIOLOGY (2022)

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Article Immunology

Microglial amyloid beta clearance is driven by PIEZO1 channels

Henna Jantti et al.

Summary: The study found that activation of the PIEZO1 channel can improve the function of microglia in Alzheimer's disease and alleviate the burden of Aβ. Pharmacological regulation of these mechanoreceptors in microglia may represent a novel therapeutic paradigm for Alzheimer's disease.

JOURNAL OF NEUROINFLAMMATION (2022)

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Article Multidisciplinary Sciences

PIEZO1 transduces mechanical itch in mice

Rose Z. Hill et al.

Summary: This study reveals that the transduction of mechanical itch is mainly mediated by the ion channel PIEZO1. Loss of PIEZO1 function greatly reduces mechanically evoked scratching behaviors and acute/chronic itch sensitization. In addition, mice expressing a gain-of-function Piezo1 allele exhibit enhanced mechanical itch behaviors.

NATURE (2022)

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Editorial Material Cardiac & Cardiovascular Systems

Piezo1 senses pressure overload and initiates cardiac hypertrophy

Gregory B. Lim

NATURE REVIEWS CARDIOLOGY (2022)

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Article Neurosciences

Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions

Shaopeng Chi et al.

Summary: This study reveals the importance of mechanotransduction mediated by Piezo1 in astrocytes for adult neurogenesis and cognitive functions. Piezo1 in astrocytes mediates mechanically evoked calcium responses and ATP release, and its deficiency leads to severe impairment in brain structure and function.

NEURON (2022)

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Article Multidisciplinary Sciences

Yoda1's energetic footprint on Piezo1 channels and its modulation by voltage and temperature

Tharaka D. Wijerathne et al.

Summary: This study comprehensively investigates the effects of Yoda1 on mouse Piezo1 channels in mammalian cells, revealing the regulatory mechanism of Yoda1 on Piezo1 channels. The study demonstrates that Yoda1 activates the channels by energetically modulating mechanosensory domains, and alters single-channel dwell times and macroscopic kinetics. Additionally, the electrophysiological effects of Yoda1 were found to depend on membrane potential and temperature.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Pharmacology & Pharmacy

Targeting endothelial ion signalling to rescue cerebral blood flow in cerebral disorders

Francesco Moccia et al.

Summary: Research has found that cerebrovascular endothelial cells play a crucial role in regulating the blood flow changes caused by neuronal activity in neurovascular coupling. These cells sense neuronal activity through ion channels and release electrical and chemical signals, resulting in vasodilation in upstream arteries. Defects in endothelial ion channels may contribute to vascular cognitive impairment and dementia.

VASCULAR PHARMACOLOGY (2022)

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Article Neurosciences

Expression of Piezo1 in the Trigeminal Neurons and in the Axons That Innervate the Dental Pulp

Yi Sul Cho et al.

Summary: This study investigated the expression of Piezo1 in the neurons and axons of the rat trigeminal ganglion (TG) and its involvement in dental mechanotransduction. The researchers found that Piezo1 was mainly expressed in medium-sized and large TG neurons, as well as in axons in the peripheral dental pulp. These findings suggest that Piezo1 plays a role in mediating acute pain elicited by high-threshold mechanical stimuli in the dental pulp.

FRONTIERS IN CELLULAR NEUROSCIENCE (2022)

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Article Multidisciplinary Sciences

A critical role of the mechanosensor PIEZO1 in glucose-induced insulin secretion in pancreatic β-cells

Yingying Ye et al.

Summary: Glucose-induced insulin secretion relies on the electrical activity of beta-cells, in which PIEZO1, a mechanosensor ion channel, plays a crucial role. Activation of PIEZO1 channel triggers beta-cell electrical activity and insulin release, while inhibition of PIEZO1 reduces these processes. Interestingly, the expression of PIEZO1 is elevated in type-2 diabetes patients and a T2D mouse model. Further investigation reveals that PIEZO1 translocates from the plasma membrane to the nucleus under high glucose conditions, resulting in its inability to influence the membrane potential of beta-cells and consequently reducing insulin secretion.

NATURE COMMUNICATIONS (2022)

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Article Cell Biology

Infection-induced membrane ruffling initiates danger and immune signaling via the mechanosensor PIEZO1

Lalitha Tadala et al.

Summary: This study demonstrates that the mechanosensitive plasma membrane channel PIEZO1 acts as a sensor for bacterial entry and initiates immune signaling through ATP secretion and gene expression. It suggests that the detection of infection by PIEZO1 is driven by physical signals instead of chemical ligands, independent of detection of microbial molecules.

CELL REPORTS (2022)

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Article Nanoscience & Nanotechnology

Piezo1 Response to Shear Stress Is Controlled by the Components of the Extracellular Matrix

Austin Lai et al.

Summary: This study investigates the influence of extracellular matrix (ECM) composition on the mechanosensitivity of the Piezo1 ion channel in response to hemodynamic forces. The presence of ECM proteins does not affect the sensitivity of Piezo1 to shear stress, but different ECM proteins regulate Piezo1 sensitivity depending on the shear stress level. These findings demonstrate that ECM/integrin interactions play a role in Piezo1 mechanosensitivity and provide new insights into how Piezo1 senses shear stress.

ACS APPLIED MATERIALS & INTERFACES (2022)

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Article Biochemistry & Molecular Biology

SYK coordinates neuroprotective microglial responses in neurodegenerative disease

Hannah Ennerfelt et al.

Summary: Recent studies have highlighted the critical roles of microglia and their receptors in controlling neurotoxic material in neurodegenerative diseases. SYK plays an important role in neuroprotective functions of microglia, with its deletion exacerbating AD deposition and neuropathology. In addition, SYK regulates microglial phagocytosis and DAM acquisition in demyelinating disease.

CELL (2022)

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Article Medicine, Research & Experimental

Fluid shear stress facilitates prostate cancer metastasis through Piezo1-Src-YAP axis

Ok-Hyeon Kim et al.

Summary: The study demonstrates that Piezo1, a mechanosensitive ion channel, is activated by WSS in microfluidic channels. Additionally, Yoda1, a Piezo1 agonist, synergistically enhances cancer cell motility and nuclear retention of YAP/TAZ via WSS. Piezo1 also increases Src phosphorylation, which activates YAP. Silencing Piezo1 significantly reduces cell motility and YAP/TAZ activity induced by WSS, ultimately slowing down tumor growth and metastasis in BALB/c mice.

LIFE SCIENCES (2022)

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Article Immunology

Ion channel Piezo1 activation promotes aerobic glycolysis in macrophages

Shaoqiu Leng et al.

Summary: Altered microenvironmental stiffness, sensed by the mechanosensitive channel Piezo1 in macrophages, can induce immune responses. This study found that Piezo1-deficient macrophages have reduced aerobic glycolysis and impaired secretion of inflammatory cytokines. Activation of Piezo1 through agonist Yoda1 or cyclical hydrostatic pressure increases glycolytic activity and enhances cytokine secretion in response to liposaccharide. In vivo, Piezo1-deficient mice are less susceptible to dextran sulfate sodium-induced colitis, while Yoda1 treatment exacerbates colitis. Mechanistically, Piezo1 activation promotes aerobic glycolysis through the Ca2+-induced CaMKII-HIF1 alpha axis. Therefore, this study demonstrates the role of Piezo1-mediated mechanosensitive signals in enhancing macrophage metabolism and immune response.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

Membrane tension propagation couples axon growth and collateral branching

Zheng Shi et al.

Summary: This study reveals that neuronal axons can remotely influence growth dynamics through rapid and long-range mechanical signaling, resulting in bidirectional competition between axonal branching and growth cone extension.

SCIENCE ADVANCES (2022)

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Article Cell Biology

A positive mechanobiological feedback loop controls bistable switching of cardiac fibroblast phenotype

Lele Niu et al.

Summary: In this study, a mutually reinforcing, mechanical positive feedback loop between integrin beta 1 and Piezol activation was discovered, forming a bistable switch. The switch can reverse the phenotypical transition of cardiac fibroblasts by modulating matrix elastic modulus, suggesting new therapeutic targets for fibrotic disease.

CELL DISCOVERY (2022)

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Article Oncology

Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma

Miao Li et al.

Summary: Piezo1 and integrin beta 1 interact with each other in hepatocellular carcinoma (HCC), promoting matrix stiffness-driven angiogenesis through Ca2+ influx and HIF-1α ubiquitination.

CANCER COMMUNICATIONS (2022)

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Article Biochemistry & Molecular Biology

Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

Yunlu Liu et al.

Summary: The biomechanical environment plays a crucial role in fracture healing, and Piezo1 is identified as a significant mechanosensor in bone homeostasis. This study demonstrates the high expression of Piezo1 in periosteal stem cells and their derived cells, and the regulation of Piezo1 can impact fracture healing. Additionally, activation of Piezo1 through specific agonist can promote fracture healing by stimulating chondrogenesis, osteogenesis, and angiogenesis, potentially making Piezo1 a therapeutic target for delayed union or nonunion fractures.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Piezo channels in the urinary system

Xu Li et al.

Summary: Understanding the role of piezo channel proteins in the urinary system could lead to novel treatments for urinary system diseases. These proteins convert mechanical signals into biological signals and mutations or disruption to them may trigger diseases. Further investigations are needed to fully understand their mechanisms of action.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

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Article Medicine, Research & Experimental

A Piezo1/KLF15/IL-6 axis mediates immobilization- induced muscle atrophy

Yu Hirata et al.

Summary: This study reveals that the upregulation of KLF15 and IL-6, as well as the decrease in intracellular Ca2+ concentration, are involved in muscle atrophy induced by immobility. This finding has been validated in both mouse models and human samples.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Multidisciplinary Sciences

Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states

Nuoying Ma et al.

Summary: This study reveals the morphological heterogeneity of muscle stem cells (MuSCs) and their different functional states. The shift between these states, regulated by the sensing protein Piezo1, promotes tissue regeneration. Activation of Piezo1 increases the responsiveness of MuSCs, while deletion of Piezo1 decreases their responsiveness. These findings enhance our understanding of how stem cells respond to injury and identify Piezo1 as a key regulator of the essential stem cell states for regeneration.

SCIENCE ADVANCES (2022)

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Article Geriatrics & Gerontology

Current characteristics and early functional outcome of older stroke patients: a population-based study (Dijon Stroke Registry)

Yannick Bejot et al.

Summary: The increasing burden of stroke in older people is associated with a greater prevalence of risk factors, severity of initial stroke, and poorer functional outcomes post-stroke among elderly patients. Discharge to home is less common in older stroke survivors, with a higher proportion requiring long-term care institutions, highlighting the need for dedicated care facilities in the future.

AGE AND AGEING (2021)

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Review Ophthalmology

Role of glia in optic nerve

Meysam Yazdankhah et al.

Summary: The optic nerve, with its unique characteristics, plays a crucial role in maintaining neuronal activity in the central nervous system. Glial cells in the optic nerve provide essential support for retinal ganglion cells and are sensitive to pathological conditions, as seen in vision problems in multiple sclerosis. Current research focuses on understanding the organization and function of glial cells in the optic nerve for potential therapeutic advances.

PROGRESS IN RETINAL AND EYE RESEARCH (2021)

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Article Cell Biology

Analyzing the shear-induced sensitization of mechanosensitive ion channel Piezo-1 in human aortic endothelial cells

Austin Lai et al.

Summary: This study used microfluidic technologies to investigate shear-induced sensitization of endothelial Piezo-1 to its selective agonist, Yoda-1, and found that the sensitization is transient and can be impaired by exposure to low and proatherogenic levels of shear stress. The process is independent of cell-cell adhesion and mediated by the PI3K-AKT signaling pathway. Additionally, shear stress was shown to increase the membrane density of Piezo-1 channels in endothelial cells.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

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Article Oncology

YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation

Kana Hasegawa et al.

Summary: The study demonstrates that the YAP signaling pathway promotes oral squamous cell carcinoma (OSCC) cell proliferation through the PIEZO1 channel, indicating a crucial role of YAP/PIEZO1 axis in tumorigenesis. These findings provide important insights into the understanding of cellular behavior changes during tumor growth.

JOURNAL OF PATHOLOGY (2021)

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Article Medicine, Research & Experimental

PIEZO1 might be involved in cerebral ischemia-reperfusion injury through ferroptosis regulation: a hypothesis

Xue-Wei Guo et al.

Summary: Stroke is linked to high mortality and disability rates, and regulating ferroptosis is a potential treatment for ischemic stroke. Research suggests that the mechanosensitive PIEZO1 channel may be involved in ischemic adaptation by regulating ferroptosis. Furthermore, the essential protein HIF1 α plays a crucial role in PIEZO1/calcium signaling and ferroptosis regulation.

MEDICAL HYPOTHESES (2021)

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Article Biochemistry & Molecular Biology

Piezo1 regulates migration and invasion of breast cancer cells via modulating cell mechanobiological properties

Yang Yu et al.

Summary: Cell migration and invasion are crucial processes during cancer metastasis. Piezo1 channel has been shown to be involved in mediating these processes in some cancers, including breast cancer. Piezo1 knockdown promotes unconfined breast cancer cell migration but impedes confined migration, and it inhibits invasion by impairing invadopodium formation and suppressing MMP expression.

ACTA BIOCHIMICA ET BIOPHYSICA SINICA (2021)

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Article Clinical Neurology

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis

Simona Schiavi et al.

Summary: This study investigated the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T, identifying significant differences in various diffusion metrics between different types of lesions and normal appearing white matter. The study also found associations between certain diffusion metrics and clinical measures, suggesting the potential clinical relevance of diffusion basis spectrum imaging in monitoring disease progression and treatment response in multiple sclerosis.

BRAIN (2021)

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Review Biochemistry & Molecular Biology

Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance

Manendra Singh Tomar et al.

Summary: This review highlights various mechanisms behind TMZ resistance, including DNA repair, miRNA involvement, drug efflux, stem cells, etc., and proposes multiple strategies for successful treatment.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2021)

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Article Neurosciences

Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease

Maria V. Sanchez-Mico et al.

Summary: In Alzheimer's disease, reactive astrocytes demonstrate reduced capacity to phagocytose and degrade dystrophic synapses, especially those containing Aβ peptides. The impairment is primarily caused by oligomeric Aβ, rather than hyperphosphorylated Tau, which directly interferes with the astrocytes' ability to clear pathological accumulations. Enhancing astrocytic phagocytosis may present a novel therapeutic approach for Alzheimer's disease.

GLIA (2021)

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Review Medicine, General & Internal

Glaucoma in Adults-Screening, Diagnosis, and Management A Review

Joshua D. Stein et al.

Summary: Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by damage to the optic nerve and retinal nerve fiber layer, leading to permanent loss of vision. Treatment involves lowering intraocular pressure through medications, laser, or surgical procedures to prevent vision loss.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Cell Biology

Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis

Xiaofei Wang et al.

Summary: The study revealed that Piezo1 plays a crucial role in gastric cancer omentum metastasis by promoting cell proliferation and migration, impacting intracellular Ca2+ influx through upregulation of HIF-1α, hence affecting tumor growth and metastasis.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021)

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Article Neurosciences

Piezo1 channels mediate trabecular meshwork mechanotransduction and promote aqueous fluid outflow

Oleg Yarishkin et al.

Summary: The trabecular meshwork is a highly mechanosensitive tissue in the eye that regulates intraocular pressure. This study identified the Piezo1 channel as a key transducer of mechanical stimuli in TM cells, shedding light on the mechanisms of intraocular pressure regulation.

JOURNAL OF PHYSIOLOGY-LONDON (2021)

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Article Medicine, Research & Experimental

Inhibiting the Piezo1 channel protects microglia from acute hyperglycaemia damage through the JNK1 and mTOR signalling pathways

Hailin Liu et al.

Summary: The study reveals that high glucose concentrations upregulate Piezo1 expression, resulting in weakened microglial cell proliferation and migration, as well as reduced immune response to inflammatory stimulating factors. Inhibiting Piezo1 may improve acute hyperglycaemia-induced cell damage, making it a potential target for treating hyperglycaemic brain injury.

LIFE SCIENCES (2021)

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Article Ophthalmology

Mechanosensitive channel inhibition attenuates TGF132-induced actin cytoskeletal remodeling and reactivity in mouse optic nerve head astrocytes

Alexander Kirschner et al.

Summary: In glaucoma, early rearrangement of actin cytoskeleton in astrocytes within the optic nerve head is associated with reactivity and ECM deposition. Inhibition of mechanosensitive channels may attenuate TGF132-mediated actin cytoskeletal remodeling in these astrocytes, suggesting a potential therapeutic strategy for glaucoma.

EXPERIMENTAL EYE RESEARCH (2021)

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Article Multidisciplinary Sciences

Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

Joon-Hyuk Lee et al.

Summary: This study demonstrates that astrocytes in the adult hippocampus carry out phagocytosis through MEGF10 to maintain proper synaptic connectivity and plasticity. The findings reveal the crucial role of astrocytes in the activity-dependent elimination of excitatory synapses, highlighting the importance of this astrocytic function in supporting cognitive function.

NATURE (2021)

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Review Clinical Neurology

Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

Fangda Leng et al.

Summary: Microglial activation and neuroinflammation play important roles in Alzheimer's disease, affecting disease progression and pathologies. Current research focuses on the interplay between neuroinflammation and amyloid and tau pathologies, with a specific interest in modulating microglia as a therapeutic strategy for AD.

NATURE REVIEWS NEUROLOGY (2021)

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Review Physiology

THE COMPLEXITY OF ALZHEIMER'SDISEASE: AN EVOLVING PUZZLE

Camilla Ferrari et al.

Summary: The history of Alzheimer's disease dates back to 1907, but it wasn't until the end of the century that the components of pathological hallmarks and genetic subtypes were identified, leading to the first pathogenic hypothesis. Advances in biomarkers and technology have shifted the concept of AD from a static view to a biological entity that can manifest in various ways. Research shows that AD is heterogeneous in terms of amyloid composition, tau distribution, clinical symptoms, and genetic background, making it difficult to explain with a single pathological process.

PHYSIOLOGICAL REVIEWS (2021)

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Review Immunology

Microglia: Immune and non-immune functions

Katharina Borst et al.

Summary: Microglia, as resident macrophages of the CNS, play crucial roles in maintaining brain homeostasis and responding to disease, through intricate bidirectional communication with other brain cells and infiltrating peripheral immune cells. This harmonious cell-cell communication is essential for maintaining tissue health and overcoming pathology such as neuroinflammation.

IMMUNITY (2021)

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Article Cell Biology

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Mainak Chakraborty et al.

Summary: This study reveals that static tension impacts immune cell function, maturation, and metabolism, with cells grown at physiological resting stiffness showing reduced proliferation, activation, and cytokine production compared to cells grown under higher stiffness. The findings suggest that mechanical stiffness is a critical environmental cue affecting dendritic cells and innate immunity.

CELL REPORTS (2021)

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Article Pharmacology & Pharmacy

Piezo 1 is involved in intraocular pressure regulation

Wataru Morozumi et al.

Summary: The study found that Piezo 1 plays a crucial role in regulating TM cell activity and may offer new insights into the treatment of glaucoma. Eye drops containing Yoda 1 reduced intraocular pressure in mice and decreased fibronectin expression level around the TM. Activation of Piezo 1 suppressed migration and proliferation of human TM cells, while increasing the expression of MMP-2 responsible for fibronectin degradation.

JOURNAL OF PHARMACOLOGICAL SCIENCES (2021)

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Article Engineering, Biomedical

Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer's disease mouse model

Nelda Antonovaite et al.

Summary: Evidence of altered tissue mechanics in neurodegeneration is increasing, especially in Alzheimer's disease. Viscoelastic differences have been found in the brain tissue of APP/PS1 mice compared to wild-type mice, with regions in the hippocampus showing increased stiffness and viscous dissipation. Despite overall mechanical heterogeneity, local alterations in stiffness were not observed at the cellular scale around the plaques.

JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Biochemistry & Molecular Biology

A role of PIEZO1 in iron metabolism in mice and humans

Shang Ma et al.

Summary: Iron overload can cause progressive organ damage and is associated with genetic factors affecting iron homeostasis. Certain individuals with hereditary disorders may develop iron overload, and some GOF PIEZO1 alleles are linked to iron imbalance. The study demonstrates the key role of PIEZO1 in macrophage phagocytic activity and iron metabolism, with a particular GOF PIEZO1 allele showing a strong association with increased plasma iron levels in individuals of African descent.

CELL (2021)

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Article Ophthalmology

Piezo1 plays a role in optic nerve head astrocyte reactivity

Jiafeng Liu et al.

Summary: Piezo1, a mechanosensing channel, plays a crucial role in the pathogenesis of neurodegenerative diseases in astrocytes. This study reveals that Piezo1 responds to mechanical stimulation and is involved in astrocyte reactivity in the optic nerve head.

EXPERIMENTAL EYE RESEARCH (2021)

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Article Multidisciplinary Sciences

Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis

Hasan Ucar et al.

Summary: The study reveals that fine and transient pushing of presynaptic boutons can significantly enhance the release of glutamate and the assembly of SNARE proteins, with effects persisting for more than 20 minutes. This enhancement is independent of cytosolic calcium, but relies on the assembly of SNARE proteins and actin polymerization in the boutons.

NATURE (2021)

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Review Medicine, General & Internal

Alzheimer's disease

Philip Scheltens et al.

Summary: Alzheimer's disease is projected to see a significant increase in prevalence in the future, with genetics playing a key role. Novel biomarkers and lifestyle-based prevention trials show promising therapeutic potential. Promising pharmacological treatments are advancing in clinical trials, targeting amyloid beta, tau, and inflammation.

LANCET (2021)

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Article Medicine, Research & Experimental

Piezo1 regulates intestinal epithelial function by affecting the tight junction protein claudin-1 via the ROCK pathway

Yudong Jiang et al.

Summary: The study revealed the regulatory role of Piezo1 in intestinal epithelial function and tight junction proteins, partially through the ROCK1/2 pathway. Piezo1 activity directly modulated epithelial function and permeability in both in vitro and ex vivo models. Activation of Piezo1 could induce epithelial dysfunction.

LIFE SCIENCES (2021)

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Article Multidisciplinary Sciences

Astrocyte Ca2+-evoked ATP release regulates myelinated axon excitability and conduction speed

Jonathan Lezmy et al.

Summary: Neuronal activity in rodents can raise intracellular calcium levels in astrocytes near myelinated axons, impacting the function of these axons and regulating information flow and neural circuit function in the brain's white matter.

SCIENCE (2021)

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Article Multidisciplinary Sciences

The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction

Fan Jiang et al.

Summary: The Piezo1 channel serves as a key cardiac mechanotransducer for converting mechanical stretch of cardiomyocytes into Ca2+ and ROS signaling to maintain normal heart function.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Mechanical stretch induces Ca2+ influx and extracellular release of PGE2 through Piezo1 activation in trabecular meshwork cells

Takatoshi Uchida et al.

Summary: The study found that Piezo1 is abundantly expressed in the trabecular meshwork and can regulate trabecular meshwork cell contraction by modulating Ca2+ influx and release of arachidonic acid and PGE(2). This suggests that Piezo1 could act as a regulator to control intraocular pressure.

SCIENTIFIC REPORTS (2021)

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Article Multidisciplinary Sciences

The role of Piezo1 in conventional aqueous humor outflow dynamics

Wei Zhu et al.

Summary: Piezo1 in the conventional aqueous humor outflow pathway plays a role in influencing intraocular pressure maintenance by activating mechanosensitive currents in trabecular meshwork cells. Interference with mechanosensitive channels can alter aqueous outflow facility and ocular compliance.

ISCIENCE (2021)

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Review Hematology

Recent advances in the pathophysiology of PIEZO1-related hereditary xerocytosis

Nicolas Jankovsky et al.

Summary: Hereditary xerocytosis is a rare red blood cell disease caused by gain-of-function mutations in the FAM38A gene, affecting PIEZO1. PIEZO1 plays a crucial role in adapting intracellular ionic content and cell hydration to mechanical stress, with recent studies revealing additional roles in erythropoiesis and other tissues.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

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Article Hematology

Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke

Ranran Wang et al.

Summary: The infusion of tPA in acute ischemic stroke increases markers of NETs in the ischemic cortex and plasma, with upregulation of PAD4 enzyme. Disruption of NETs or inhibition of cGAS may reduce tPA-associated hemorrhage and BBB breakdown, suggesting potential therapeutic targets for thrombolytic therapy in ischemic stroke.

BLOOD (2021)

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Article Cell Biology

Piezo1 impairs hepatocellular tumor growth via deregulation of the MAPK-mediated YAP signaling pathway

Silin Liu et al.

Summary: The study revealed the crucial role of Piezo1 in HCC, showing that activation of the MAPK/YAP signaling cascade controls tumor cell growth and migration, highlighting its significance as a potential biomarker and therapeutic target.

CELL CALCIUM (2021)

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Article Neurosciences

Differential effects of the Piezo1 agonist Yoda1 in the trigeminovascular system: An electrophysiological and intravital microscopy study in rats

Antonina Dolgorukova et al.

Summary: Migraine is associated with the activation and sensitization of the trigeminovascular system. Piezo1, expressed in endothelial cells and trigeminal ganglion neurons, may play a role in both vascular and neuronal activation. Activation of Piezo1 channels can modulate both neuronal firing and vascular dilation, providing new evidence for its involvement in migraine pathogenesis.

EXPERIMENTAL NEUROLOGY (2021)

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Article Oncology

YAP promotes autophagy and progression of gliomas via upregulating HMGB1

Min Zhao et al.

Summary: YAP over-expression enhances glioma cell autophagy and progression by promoting the translocation of HMGB1 from nucleus to cytoplasm, suggesting a potential therapeutic target in GBM. The combination of chemo-radiotherapy with pharmacological autophagy inhibition for treating GBM patients with YAP high expression may be a promising clinical opportunity.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Article Immunology

Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin

Thecla A. van Wageningen et al.

Summary: The biomechanical properties of microglia derived from white matter (WM) and gray matter (GM) show significant differences, with WM-derived microglia being more elastic and viscous than GM-derived microglia. Additionally, the response to inflammation and demyelination varies between WM- and GM-derived microglia.

JOURNAL OF NEUROINFLAMMATION (2021)

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Review Pharmacology & Pharmacy

Channeling Force in the Brain: Mechanosensitive Ion Channels Choreograph Mechanics and Malignancies

Ali Momin et al.

Summary: Cells generate, transmit, and sense mechanical forces, shaping the mechanical properties of cells and tissues; in the brain, disrupted mechanical properties are observed in cancer states. Mechanosensitive ion channels govern ion flux and cellular signaling in response to mechanical cues, offering insights for therapeutic opportunities in brain tumors at the interface of cancer, neuroscience, and mechanobiology.

TRENDS IN PHARMACOLOGICAL SCIENCES (2021)

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Article Acoustics

Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles

Xuelian Shen et al.

Summary: The study shows that by developing Piezo1-targeted microbubbles, the energy requirement for cellular response to ultrasound stimulation can be significantly reduced, making ultrasound-mediated neuromodulation safer and more efficient. Ultrasound can mediate calcium influx through Piezo1 channels, and the presence of bubbles does not lead to significant destruction or heating effects.

ULTRASONICS SONOCHEMISTRY (2021)

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Article Multidisciplinary Sciences

Temporal analysis of T-cell receptor-imposed forces via quantitative single molecule FRET measurements

Janett Goehring et al.

Summary: This study introduces a FRET-based sensor that directly measures the magnitude and kinetics of forces imposed by TCR at the single molecule level. Results showed that when T cells were confronted with gel-phase SLBs, there was a single force peak of around 5pN prior and upon activation, with force loading rates around 1.5pN per second on the TCR; while facing fluid-phase SLBs, T cells exerted tensile forces prior to activation but not afterwards, although of reduced magnitude compared to gel-phase SLBs.

NATURE COMMUNICATIONS (2021)

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Article Physiology

Time window effect of Yoda1-evoked Piezo1 channel activity during mouse skeletal muscle differentiation

Alessandra Bosutti et al.

Summary: Chemical activation of Piezo1 channels enhances the differentiation of skeletal muscle precursors, while showing no significant impact on adult muscle fibers and neuromuscular junctions. This suggests a potential new strategy for promoting muscle regeneration.

ACTA PHYSIOLOGICA (2021)

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Review Cell Biology

Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease

Brittani R. Price et al.

Summary: Astrocyte reactivity is a key feature of neuroinflammation in Alzheimer's disease and other neurodegenerative conditions, with roles extending beyond classic inflammatory processes to include synapse function, brain metabolism, neurovascular coupling, and sleep/wake patterns. Understanding astrocyte signaling is leading to new drug targets and treatment approaches for dementia, potentially reshaping our understanding of AD pathophysiology.

AGEING RESEARCH REVIEWS (2021)

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Article Engineering, Biomedical

Multiscale rheology of glioma cells

Charlotte Alibert et al.

Summary: Cells tend to soften during cancer progression, and mechanical phenotyping could be used as a diagnostic or prognostic method. By investigating the cell mechanics of gliomas, research shows that cell mechanics discriminates human glioma cells of different grades, suggesting the potential of combining rheology techniques for cancer cell mechanophenotyping in diagnostic or prognostic methods.

BIOMATERIALS (2021)

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Article Oncology

The ever-increasing importance of cancer as a leading cause of premature death worldwide

Freddie Bray et al.

Summary: CVD and cancer are now leading causes of premature death in 127 countries with cancer poised to overtake CVD in most countries over the course of this century. Governments must consider these transitions in disease profiles when developing cancer policies at the local level.

CANCER (2021)

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Article Cell Biology

Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair

Peng Chen et al.

Summary: Piezo1, a calcium-permeable non-selective cationic channel, plays a crucial role in sensing mechanical stimulation in multicellular organisms, mediating angiogenesis and bone fracture repair processes. Deletion of endothelial Piezo1 may impair bone fracture repair, affecting various biological processes and signaling pathways.

CELL CALCIUM (2021)

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Article Peripheral Vascular Disease

Piezo1-Mediated Mechanotransduction Promotes Cardiac Hypertrophy by Impairing Calcium Homeostasis to Activate Calpain/Calcineurin Signaling

Yuhao Zhang et al.

Summary: Hemodynamic overload leads to pathological cardiac hypertrophy, which is a major risk factor for heart failure. Piezo1, a novel mechanosensitive ion channel, plays a crucial role in the development of cardiac hypertrophy and may be a potential therapeutic target for cardiac dysfunction.

HYPERTENSION (2021)

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Article Hematology

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension

Weiyu Zhao et al.

Summary: The activation of mechanoreceptor Piezo1 under hypertension is crucial for abnormal platelet activation and thrombosis, while inhibition of Piezo1 can effectively prevent arterial thrombosis caused by hypertension.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2021)

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Article Multidisciplinary Sciences

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis

Martina Absinta et al.

Summary: Through MRI-guided single-nucleus RNA sequencing, a diversity of glial and immune cells at the edge of demyelinated white matter lesions in multiple sclerosis (MS) have been identified, along with the definition of inflamed glial cell phenotypes in MS. The overlap of the transcriptional profile of microglia inflamed in MS with that in other neurodegenerative diseases suggests common mechanisms between primary and secondary neurodegeneration that could benefit from similar therapeutic approaches. The critical role of complement component 1q (C1q) in the activation of microglia inflamed in MS has been identified and potential therapeutic avenues, such as C1q inhibition, have been suggested for addressing chronic white matter inflammation.

NATURE (2021)

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Article Immunology

Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity

Wei Hu et al.

Summary: Regulatory T cells play a crucial role in preventing fatal autoimmune inflammation, exerting their function in settings of established broad-spectrum systemic inflammation, and enabling sustained reset of immune homeostasis.

NATURE IMMUNOLOGY (2021)

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Review Neurosciences

Revisiting the neurovascular unit

Samantha Schaeffer et al.

Summary: Schaeffer and Iadecola reviewed the heterogeneity of the neurovasculature and discussed the limitations of the neurovascular unit concept and the molecular diversity of cerebrovascular cells. They proposed the concept of a 'neurovascular complex' composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals.

NATURE NEUROSCIENCE (2021)

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Review Ophthalmology

Aqueous outflow regulation-21st century concepts

Murray Johnstone et al.

Summary: The article proposes an integrated model of aqueous outflow control using a pump-conduit system, drawing on physiological regulatory mechanisms to improve care for glaucoma patients. The model focuses on trabecular meshwork distention and recoil, with inlet and outlet valves controlling aqueous flow from Schlemm's canal. The failure of the aqueous outflow pump in glaucoma is attributed to loss of tissue elastance and alterations in ciliary body tension, leading to SC wall apposition and reduced pulsatile aqueous discharge. Monitoring these alterations clinically is challenging, but phase-sensitive OCT offers a noninvasive way to measure pulse-dependent TM motion in humans, providing a novel framework for understanding mechanisms and therapeutic options for glaucoma.

PROGRESS IN RETINAL AND EYE RESEARCH (2021)

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Review Multidisciplinary Sciences

Architectures of neuronal circuits

Liqun Luo

Summary: While individual neurons are the building blocks of the nervous system, they function by collaborating in neuronal circuits with specific patterns of synaptic connectivity. Understanding how these circuits assemble and evolve can help bridge the gap between individual neuron biology and brain function, leading to insights into neural computations and behavior.

SCIENCE (2021)

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Article Clinical Neurology

Mechanical Characterization of Thrombi Retrieved With Endovascular Thrombectomy in Patients With Acute Ischemic Stroke

Nikki Boodt et al.

Summary: In this study, mechanical properties of thrombi retrieved with EVT in acute stroke patients were analyzed, revealing a strong association between fibrin/platelet content and thrombus stiffness, as well as impacts of erythrocytes and platelets on thrombus stiffness. These findings provide a basis for future research and development of next-generation EVT devices tailored to thrombus composition.

STROKE (2021)

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Article Multidisciplinary Sciences

TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection

Jing Geng et al.

Summary: TLR4 signaling enhances macrophage bactericidal activity through the mechanical sensor Piezo1, with mechanical sensing signals playing a critical role in the innate immune response. The assembly of Piezo1 and TLR4 complex triggers the remodeling of F-actin organization to augment phagocytosis and bacterial clearance, providing insights into macrophage mechanophysiology and host response coordination.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

Hamza Atcha et al.

Summary: Studies reveal that Piezo1 serves as a mechanosensor of stiffness in macrophages, influencing their polarization responses.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation

Feng Li et al.

Summary: The Atr-Chek1 pathway, involved in cell cycle and DNA damage response, inhibits axon regeneration in response to Piezo-mediated mechanosensation, affecting functional recovery. Targeting this pathway could potentially be useful for treating nervous system trauma.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

The neurodynamic treatment induces biological changes in sensory and motor neurons in vitro

Giacomo Carta et al.

Summary: The study confirms significant effects of neurodynamic treatment (NDT) on sensory neurons, promoting cell differentiation, neurite outgrowth, and neuron survival, especially in nociceptive neurons.

SCIENTIFIC REPORTS (2021)

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Article Cell Biology

Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback

Jordan N. Haidey et al.

Summary: The study reveals that enhancing tone can trigger a Ca2+ elevation in astrocyte end-feet, leading to feedback vasodilators that limit vasoconstriction and constrain vasomotion. Additionally, in vivo experiments show that knocking out the Ptgs1 gene in astrocytes increases the energy of arteriole oscillations, while clamping astrocyte Ca2+ decreases vasomotion energy.

CELL REPORTS (2021)

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Article Immunology

Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues

Hamza Atcha et al.

Summary: The study demonstrates that both cyclic and static stretch influence macrophage morphology and responses to different stimuli. The integrin CD11b and ion channel Piezo1 may play a role in mechanotransduction in macrophages.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Engineering, Biomedical

Shear-stress sensing by PIEZO1 regulates tendon stiffness in rodents and influences jumping performance in humans

Fabian S. Passini et al.

Summary: This study found that tenocytes detect mechanical forces through the mechanosensitive ion channel PIEZO1, influencing tendon stiffness and strength. Humans carrying specific mutations in PIEZO1 may exhibit higher athletic performance.

NATURE BIOMEDICAL ENGINEERING (2021)

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Review Biochemistry & Molecular Biology

Extracellular matrix and its therapeutic potential for cancer treatment

Jiacheng Huang et al.

Summary: The extracellular matrix (ECM) is a key component of tumors, playing roles in mechanical support, microenvironment modulation, and signaling. Interactions between cancer cells and the tumor microenvironment can lead to ECM stiffness changes and contribute to malignant transformation. Understanding ECM dysregulation in the TME is essential for identifying therapeutic targets for cancer treatment.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Cell & Tissue Engineering

Piezo1 channel activation in response to mechanobiological acoustic radiation force in osteoblastic cells

Guangdao Zhang et al.

Summary: The mechanosensitive ion channel Piezo1 is believed to play a crucial role in transducing mechanical signals induced by LIPUS to regulate cell migration and proliferation. Experimental results indicate that Piezo1 can modulate intracellular calcium levels in response to LIPUS stimulation, affecting the growth processes of cells.

BONE RESEARCH (2021)

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Review Cell Biology

Crosstalk between mechanotransduction and metabolism

Patrizia Romani et al.

Summary: Mechanical forces play a crucial role in regulating cell function and behavior by modulating cell metabolism and impacting tissue mechanics. Recent evidence suggests that mechanical cues from the extracellular matrix and cell adhesion complexes influence metabolic pathways, highlighting the reciprocal crosstalk between cell mechanics and metabolism.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Article Neurosciences

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Maria Velasco-Estevez et al.

GLIA (2020)

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Article Cell Biology

Manipulation of Mitophagy by All-in-One nanosensitizer augments sonodynamic glioma therapy

Fei Qu et al.

AUTOPHAGY (2020)

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Article Neurosciences

Inhibition of Piezo1 attenuates demyelination in the central nervous system

Maria Velasco-Estevez et al.

GLIA (2020)

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Article Clinical Neurology

Overlapping genetic architecture between Parkinson disease and melanoma

Umber Dube et al.

ACTA NEUROPATHOLOGICA (2020)

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Article Hematology

Gain-of-function mutations in PIEZO1 directly impair hepatic iron metabolism via the inhibition of the BMP/SMADs pathway

Immacolata Andolfo et al.

AMERICAN JOURNAL OF HEMATOLOGY (2020)

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Review Immunology

Regulatory T Cells and Human Disease

Shimon Sakaguchi et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 38 (2020)

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Review Neurosciences

Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms

Peng Jin et al.

ANNUAL REVIEW OF NEUROSCIENCE, VOL 43 (2020)

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Article Biochemistry & Molecular Biology

Mapping the Fine-Scale Organization and Plasticity of the Brain Vasculature

Christoph Kirst et al.

CELL (2020)

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Review Immunology

Innate sensing of mechanical properties of brain tissue by microglia

Pinar Ayata et al.

CURRENT OPINION IN IMMUNOLOGY (2020)

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Article Ophthalmology

Piezo channel plays a part in retinal ganglion cell damage

Wataru Morozumi et al.

EXPERIMENTAL EYE RESEARCH (2020)

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Article Biochemistry & Molecular Biology

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

Cornelia Bratengeier et al.

FASEB JOURNAL (2020)

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Article Neurosciences

mTOR-mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP

Yaling Hu et al.

GLIA (2020)

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Article Neurosciences

Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory

Fei Wang et al.

NATURE NEUROSCIENCE (2020)

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Article Public, Environmental & Occupational Health

Global, Regional and Country-Specific Burden of Ischaemic Stroke, Intracerebral Haemorrhage and Subarachnoid Haemorrhage: A Systematic Analysis of the Global Burden of Disease Study 2017

Rita Krishnamurthi et al.

NEUROEPIDEMIOLOGY (2020)

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Article Multidisciplinary Sciences

Neurons differentiate magnitude and location of mechanical stimuli

Benjamin M. Gaub et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Multidisciplinary Sciences

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Lijun Wang et al.

NATURE COMMUNICATIONS (2020)

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Article Cell Biology

Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

Handong Ma et al.

CELL REPORTS (2020)

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Article Medicine, Research & Experimental

TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation

Sandip M. Swain et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Neurosciences

Glaucoma as a Neurodegenerative Disease Caused by Intrinsic Vulnerability Factors

Ana Artero-Castro et al.

PROGRESS IN NEUROBIOLOGY (2020)

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Article Pharmacology & Pharmacy

Tubeimoside I Antagonizes Yoda1-Evoked Piezo1 Channel Activation

Silin Liu et al.

FRONTIERS IN PHARMACOLOGY (2020)

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Article Oncology

Upregulation of Piezo1 Is a Novel Prognostic Indicator in Glioma Patients

Shanqiang Qu et al.

CANCER MANAGEMENT AND RESEARCH (2020)

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Article Clinical Neurology

Effect of Piezo1 Overexpression on Peritumoral Brain Edema in Glioblastomas

S. Qu et al.

AMERICAN JOURNAL OF NEURORADIOLOGY (2020)

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Review Cell Biology

Integrating Chemistry and Mechanics: The Forces Driving Axon Growth

Kristian Franze

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 36, 2020 (2020)

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Article Engineering, Biomedical

Bile canaliculi contract autonomously by releasing calcium into hepatocytes via mechanosensitive calcium channel

Kapish Gupta et al.

BIOMATERIALS (2020)

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Article Biochemistry & Molecular Biology

Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

Kathrin Diem et al.

FASEB JOURNAL (2020)

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Article Biochemistry & Molecular Biology

RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis

Erika Sugisawa et al.

CELL (2020)

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Article Medicine, General & Internal

Stroke

Bruce C V Campbell et al.

LANCET (2020)

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Article Biochemistry & Molecular Biology

HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

Jian Wang et al.

CELL (2020)

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Correction Neurosciences

Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles (vol 23, pg 561, 2020)

Anusha Mishra et al.

NATURE NEUROSCIENCE (2020)

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Article Chemistry, Multidisciplinary

Biomimicking Fiber Platform with Tunable Stiffness to Study Mechanotransduction Reveals Stiffness Enhances Oligodendrocyte Differentiation but Impedes Myelination through YAP-Dependent Regulation

William Ong et al.

SMALL (2020)

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Article Immunology

Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge

Anat Shemer et al.

IMMUNITY (2020)

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Review Neurosciences

Making sense of astrocytic calcium signals - from acquisition to interpretation

Alexey Semyanov et al.

NATURE REVIEWS NEUROSCIENCE (2020)

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Article Neurosciences

Piezo1-Mediated Ca2+ Activities Regulate Brain Vascular Pathfinding during Development

Ting-ting Liu et al.

NEURON (2020)

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Article Multidisciplinary Sciences

How cholesterol stiffens unsaturated lipid membranes

Saptarshi Chakraborty et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Review Immunology

Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity

Michael V. Sofroniew

TRENDS IN IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

Identification of PIEZO1 as a potential prognostic marker in gliomas

Wenjianlong Zhou et al.

SCIENTIFIC REPORTS (2020)

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Article Medicine, Research & Experimental

Activation of Piezo1 by ultrasonic stimulation and its effect on the permeability of human umbilical vein endothelial cells

Liguo Zhang et al.

BIOMEDICINE & PHARMACOTHERAPY (2020)

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Article Neurosciences

Mechanosensory Signaling in Astrocytes

Egor A. Turovsky et al.

JOURNAL OF NEUROSCIENCE (2020)

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Article Multidisciplinary Sciences

Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice

Sally L. Baxter et al.

SCIENTIFIC REPORTS (2020)

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Article Materials Science, Biomaterials

Substrate stiffness induced mechanotransduction regulates temporal evolution of human fetal neural progenitor cell phenotype, differentiation, and biomechanics

Chandrasekhar Kothapalli et al.

BIOMATERIALS SCIENCE (2020)

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Article Neuroimaging

Hippocampal stiffness in mesial temporal lobe epilepsy measured with MR elastography: Preliminary comparison with healthy participants

Graham R. Huesmann et al.

NEUROIMAGE-CLINICAL (2020)

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Article Cell Biology

Src mediates TGF-β-induced intraocular pressure elevation in glaucoma

Teruhisa Tsukamoto et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2019)

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Review Neurosciences

Mechano-modulation of nuclear events regulating oligodendrocyte progenitor gene expression

Eric Tsai et al.

GLIA (2019)

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Article Neurosciences

The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

Yuanquan Song et al.

NEURON (2019)

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Article Multidisciplinary Sciences

Dietary fatty acids fine-tune Piezo1 mechanical response

Luis O. Romero et al.

NATURE COMMUNICATIONS (2019)

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Article Cell Biology

Mechanically Activated Piezo Channels Mediate Touch and Suppress Acute Mechanical Pain Response in Mice

Mingmin Zhang et al.

CELL REPORTS (2019)

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Article Biochemistry & Molecular Biology

Piezol mediates neuron oxygen-glucose deprivation/reoxygenation injury via Ca2+/calpain signaling

Ying-Ying Wang et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2019)

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Article Biochemistry & Molecular Biology

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke

Ishraq Alim et al.

CELL (2019)

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Review Clinical Neurology

The role of astroglia in Alzheimer's disease: pathophysiology and clinical implications

Amaia M. Arranz et al.

LANCET NEUROLOGY (2019)

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Article Neurosciences

Mechanosensitive meningeal nociception via Piezo channels: Implications for pulsatile pain in migraine?

Nikita Mikhailov et al.

NEUROPHARMACOLOGY (2019)

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Review Neurosciences

Microglia: Brain cells on the move

Sophie Marie-Therese Smolders et al.

PROGRESS IN NEUROBIOLOGY (2019)

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Article Genetics & Heredity

A Systems Analysis of the Relationships Between Anemia and Ischemic Stroke Rehabilitation Based on RNA-Seq Data

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Review Physiology

MYELIN IN THE CENTRAL NERVOUS SYSTEM: STRUCTURE, FUNCTION, AND PATHOLOGY

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Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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PIEZO1 Is Selectively Expressed in Small Diameter Mouse DRG Neurons Distinct From Neurons Strongly Expressing TRPV1

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FRONTIERS IN MOLECULAR NEUROSCIENCE (2019)

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Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity

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Force-induced conformational changes in PIEZO1

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Niche stiffness underlies the ageing of central nervous system progenitor cells

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Unconventional Roles of Cytoskeletal Mitotic Machinery in Neurodevelopment

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Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

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Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

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Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

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Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology

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TRENDS IN MOLECULAR MEDICINE (2019)

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Optic Nerve Head Astrocytes Display Axon-Dependent and-Independent Reactivity in Response to Acutely Elevated Intraocular Pressure

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The Mechanosensitive Ion Channel Piezo1 Significantly Mediates In Vitro Ultrasonic Stimulation of Neurons

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Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers

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Characterization of Biaxial Stretch as an In Vitro Model of Traumatic Brain Injury to the Blood-Brain Barrier

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Structure of the mechanically activated ion channel Piezol

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Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation

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Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation

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Stretch-induced Ca2+ independent ATP release in hippocampal astrocytes

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Microglial control of astrocytes in response to microbial metabolites

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Structure and mechanogating mechanism of the Piezol channel

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Heterogeneous Cytoskeletal Force Distribution Delineates the Onset Ca2+ Influx Under Fluid Shear Stress in Astrocytes

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Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis

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A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel

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Probing the gating mechanism of the mechanosensitive channel Piezol with the small molecule Yoda1

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Alzheimer's Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

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Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation

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A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression

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Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation

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Glia as architects of central nervous system formation and function

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Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes

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Sonodynamic therapy induces oxidative stress, DNA damage and apoptosis in glioma cells

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YAP Functions as a Mechanotransducer in Oligodendrocyte Morphogenesis and Maturation

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Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line

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Role of Piezo Channels in Ultrasound-stimulated Dental Stem Cells

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β-catenin-mediated YAP signaling promotes human glioma growth

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Mechanical Stimulation of Piezo1 Receptors Depends on Extracellular Matrix Proteins and Directionality of Force

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Mechanical forces direct stem cell behaviour in development and regeneration

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A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

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Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance

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MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias

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Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D

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CARDIOVASCULAR RESEARCH (2017)

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GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels

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Brain stiffness increases with myelin content

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Mechanotransduction of the endothelial glycocalyx mediates nitric oxide production through activation of TRP channels

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Mechanosensing is critical for axon growth in the developing brain

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Regional brain stiffness changes across the Alzheimer's disease spectrum

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A Threshold Shear Force for Calcium Influx in an Astrocyte Model of Traumatic Brain Injury

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Architecture of the mammalian mechanosensitive Piezol channel

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Microglia mechanics: immune activation alters traction forces and durotaxis

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Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis

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Review Clinical Neurology

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The Pathophysiology and Treatment of Glaucoma A Review

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Piezol integration of vascular architecture with physiological force

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Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040 A Systematic Review and Meta-Analysis

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Stochastic nanoroughness modulates neuron-astrocyte interactions and function via mechanosensing cation channels

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Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

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Site- Specifi c Differentiation of Neural Stem Cell Regulated by Micropatterned Multicomponent Interfaces

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Astrocytic Adenosine 5′-Triphosphate Release Regulates the Proliferation of Neural Stem Cells in the Adult Hippocampus

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Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels

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Critical role of TRPP2 and TRPC1 channels in stretch-induced injury of blood-brain barrier endothelial cells

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Piezo proteins are pore-forming subunits of mechanically activated channels

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The role of Drosophila Piezo in mechanical nociception

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Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography

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The Mechanosensitive Ion Channel Piezo1 Is Inhibited by the Peptide GsMTx4

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Mechanosensitivity of astrocytes on optimized polyacrylamide gels analyzed by quantitative morphometry

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Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels

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Equal Numbers of Neuronal and Nonneuronal Cells Make the Human Brain an Isometrically Scaled-Up Primate Brain

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Ablation of cholesterol biosynthesis in neural stem cells increases their VEGF expression and angiogenesis but causes neuron apoptosis

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Tripartite synapses: astrocytes process and control synaptic information

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YAP regulates neural progenitor cell number via the TEA domain transcription factor

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A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes

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Matrix elasticity directs stem cell lineage specification

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