☆ 4.6 Review

The fibrogenic niche in kidney fibrosis: components and mechanisms

NATURE REVIEWS NEPHROLOGY (2022)

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Review Urology & Nephrology

Ageing, cellular senescence and chronic kidney disease: experimental evidence

Huishi Tan et al.

Summary: This review summarizes the experimental evidence linking cellular senescence to the pathobiology of kidney ageing and CKD, and discusses strategies for targeting senescent cells in developing therapeutics for ageing-related kidney disorders.

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION (2022)

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Article Pharmacology & Pharmacy

Secreted protein acidic and rich in cysteine (SPARC) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) increments by the renin-angiotensin system induce renal fibrosis in deoxycorticosterone acetate-salt hypertensive rats

Hiroe Toba et al.

Summary: This study investigated the role of SPARC and ADAMTS1 in renal fibrosis using a rat model. The treatment with DOCA and salt induced kidney damage and fibrosis, and increased the expression of SPARC and ADAMTS1, promoting collagen deposition and fibrosis progression. The angiotensin II type-1 receptor blocker losartan suppressed the overexpression of SPARC and ADAMTS1, thereby slowing down fibrosis development.

EUROPEAN JOURNAL OF PHARMACOLOGY (2022)

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Article Biochemistry & Molecular Biology

Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease

Xiaoli Sun et al.

Summary: MMP-10 is an endopeptidase involved in degradation of extracellular matrices and plays different roles in kidney diseases. It is also a potential therapeutic target in renal cell carcinoma.

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Article Multidisciplinary Sciences

A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-β signaling

Qian Yuan et al.

Summary: Loss of Klotho protein is involved in the development of chronic kidney diseases. Researchers have discovered a peptide called KP1 derived from Klotho protein that protects the kidneys by targeting the TGF-beta signaling pathway. KP1 inhibits TGF-beta signaling, prevents fibrosis, and improves kidney function.

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Article Medicine, Research & Experimental

CXCR4 induces podocyte injury and proteinuria by activating β-catenin signaling

Hongyan Mo et al.

Summary: This study found that CXCR4 and beta-catenin colocalized in glomerular podocytes and that the assembly of CXCR4/beta-arrestin-1/Src signalosome led to beta-catenin activation, promoting podocyte dysfunction and proteinuria.

THERANOSTICS (2022)

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Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition

Philip Chiu-Tsun Tang et al.

Summary: This study identified a novel role of macrophage-myofibroblast transition (MMT) in cancer, showing that MMT cells can de novo generate cancer-promoting cancer-associated fibroblasts (CAFs). Through fate-mapping, RNA velocity, and pseudotime analysis, a subset of CAFs derived from macrophages was confirmed in the tumor microenvironment. Targeting Smad3, a key regulator in the MMT process, effectively blocked CAF formation and cancer progression in vivo, suggesting MMT as a potential therapeutic target for cancer immunotherapy.

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Review Biochemistry & Molecular Biology

Computational modelling of stem cell-niche interactions facilitates discovery of strategies to enhance tissue regeneration and counteract ageing

Ilya Potapov et al.

Summary: The stem cell niche is crucial for maintaining genuine quiescent stem cells in adult tissues, with potential deteriorations in extremely old age. Computational tool NicheHotSpotter plays a key role in identifying niche and cell signalling factors for rejuvenating strategies. By analyzing the interaction between stem cells and their microenvironment, novel approaches to enhance stemness and rejuvenate skeletal muscle cells at an advanced age have been discovered.

FEBS JOURNAL (2022)

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Review Pediatrics

Hyaluronan, a double-edged sword in kidney diseases

Aditya Kaul et al.

Summary: Hyaluronic acid plays a dual role in kidney diseases, promoting both fibrotic and anti-fibrotic events depending on its molecular weight. It is induced during the initial response phase of kidney injury but decreases as diseases progress like AKI, CKD, and diabetic nephropathy.

PEDIATRIC NEPHROLOGY (2022)

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Article Cell Biology

β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis

Shuangqin Chen et al.

Summary: The activation of beta-catenin in renal tubular cells leads to the release of exosomes containing osteopontin (OPN) that are then taken up by fibroblasts, promoting their proliferation and activation through binding with CD44. Deletion of beta-catenin or CD44 greatly improves renal fibrosis. N-terminal fragment of OPN is secreted into the urine and negatively correlated with kidney function in CKD patients. Urinary exosomes from CKD patients accelerate renal fibrosis, which can be blocked by CD44 deletion.

JOURNAL OF EXTRACELLULAR VESICLES (2022)

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Review Medicine, General & Internal

New Aspects of Kidney Fibrosis-From Mechanisms of Injury to Modulation of Disease

Marcus J. Moeller et al.

Summary: Organ fibrogenesis, characterized by a common pathophysiological final pathway, independent of the progressive disease, offers potential therapeutic targets. The SFB/TRR57 consortium successfully identified new mechanisms and established novel therapeutic approaches to interfere with hepatic and renal fibrosis. This review focuses on the consortium's key findings related to renal fibrosis, addressing new relevant mechanisms, immunological contributors, and modulation strategies.

FRONTIERS IN MEDICINE (2022)

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Article Critical Care Medicine

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis A Clinical Trial

Steven L. Brody et al.

Summary: The Cu-64-DOTA-ECL1i PET uptake correlated with CCR2(+) cell infiltration in the lung associated with fibrosis, with inhibition of fibrosis by IL1 beta blockade or pirfenidone reducing CCR2(+) macrophage accumulation. CCR2(+) cells concentrated in perifibrotic regions in lung tissues from patients with IPF, exhibiting intensive signals in fibrotic zones compared to healthy volunteers. These findings suggest a role for imaging CCR2(+) cells within the fibrogenic niche in IPF for personalized therapy and monitoring.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

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Review Dermatology

The fibrillin microfibril/elastic fibre network: A critical extracellular supramolecular scaffold to balance skin homoeostasis

Christin S. Adamo et al.

Summary: Supramolecular networks composed of fibrillins and associated ligands play a crucial role in balancing skin homoeostasis and directing remodeling, influencing skin elasticity and growth factor availability. Fibrillin microfibrils are essential for elastic fiber formation and contribute to skin pliability. Mutations in fibrillin genes can lead to a wide range of skin phenotypes, with FMF regulating growth factor signaling critical for skin growth and homoeostasis.

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Review Urology & Nephrology

WNT-β-catenin signalling - a versatile player in kidney injury and repair

Stefan J. Schunk et al.

Summary: The WNT-beta-catenin pathway plays a critical role in kidney development and repair, with transient activation aiding in tissue regeneration after acute kidney injury, but uncontrolled signalling can lead to kidney fibrosis and other kidney diseases.

NATURE REVIEWS NEPHROLOGY (2021)

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Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

Yunfan Sun et al.

Summary: This study showed that early-relapse hepatocellular carcinoma (HCC) tumors exhibit innate-like CD8(+) T cells with overexpression of KLRB1 (CD161) and a low cytotoxic state, unlike the exhausted state seen in primary HCC. These cells were associated with a worse prognosis. Additionally, potential immune evasion mechanisms were identified in recurrent tumor cells, which dampen dendritic cell antigen presentation and recruit innate-like CD8(+) T cells.

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Assessment of a computerized quantitative quality control tool for whole slide images of kidney biopsies

Yijiang Chen et al.

Summary: This study evaluated a computer-aided QC pipeline for enhancing reproducibility in the QC process of WSI datasets, showing improvements in curation consistency and detection of batch effects.

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Matrix metalloproteinase-10 protects against acute kidney injury by augmenting epidermal growth factor receptor signaling

Chengxiao Hu et al.

Summary: MMP-10 plays a protective role in AKI by enhancing EGFR signaling, leading to promotion of tubular cell survival and proliferation after injury.

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Identification of matrix metalloproteinase-10 as a key mediator of podocyte injury and proteinuria

Yangyang Zuo et al.

Summary: Research revealed that MMP-10 could induce podocyte injury by degrading ZO-1, thereby promoting proteinuria and chronic diseases.

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Viktor Zaykov et al.

Summary: CCN2/CTGF is a multifunctional protein that regulates diverse cellular processes including adhesion, proliferation, apoptosis, and extracellular matrix synthesis, with different effects on developmental and pathological processes. It interacts with cell surface receptors, growth factors, and ECM proteins to elicit various cellular responses, highlighting its complexity and tissue-specific effects. Discovery of new binding partners may provide insights into unknown roles of CCN2/CTGF for potential therapeutic targeting.

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MicroRNA-10 negatively regulates inflammation in diabetic kidney via targeting activation of the NLRP3 inflammasome

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Review Urology & Nephrology

Key metalloproteinase-mediated pathways in the kidney

Justyna Wozniak et al.

Summary: Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs) play important roles in kidney diseases and could be therapeutic targets. Research has shown that these proteases are associated with profibrotic pathways involving various signaling pathways. Targeted approaches against these proteases may offer better treatment outcomes.

NATURE REVIEWS NEPHROLOGY (2021)

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LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence

Qian Ren et al.

Summary: LRP5 and LRP6 are crucial in mediating Wnt signaling, with similar functions but also distinct characteristics, as they interact with different protein partners, each possessing its own unique functions. Understanding the precise roles of LRP5 and LRP6 may help in identifying and refining therapeutic targets for various human diseases.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Cell Biology

The Extracellular Matrix Glycoprotein Tenascin C and Adult Neurogenesis

Milena Tucic et al.

Summary: TnC plays a crucial role in regulating cell proliferation and migration during adult neurogenesis, with implications for regenerative therapies. Understanding ECM signaling in the CNS niche is essential for potential therapeutic applications.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Medicine, Research & Experimental

Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis

Sandra Rayego-Mateos et al.

Summary: Chronic kidney disease is characterized by the accumulation of ECM proteins in renal structures, leading to tubulointerstitial fibrosis. Understanding the cellular and molecular mechanisms involved in kidney fibrosis, including ECM components, profibrotic factors, and cell-matrix interactions, can help improve antifibrotic therapies for CKD. Matricellular proteins, such as CCN2, play a key role in regulating cell-ECM interactions and cellular phenotype changes in kidney fibrosis.

CLINICAL SCIENCE (2021)

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Article Cell Biology

Recent advancements in decellularized matrix technology for bone tissue engineering

Mohammadreza Safdari et al.

Summary: Decellularized ECM technology provides a biomimetic scaffold for tissue engineering, promoting cell adhesion, growth, and differentiation. Decellularization is mediated through physical, chemical, and enzymatic methods. This technology has wide applications in bone repair and regeneration.

DIFFERENTIATION (2021)

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Article Urology & Nephrology

Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis

Insa M. Schmidt et al.

Summary: Analysis of gene expression profiles and the development of Luminex-based assays were used to identify promising non-invasive biomarkers of kidney fibrosis. CDH11, SMOC2, and PEDF were found to be associated with the severity of interstitial fibrosis and tubular atrophy, as well as progression to end-stage kidney disease in independent cohorts of chronic kidney disease patients.

KIDNEY INTERNATIONAL (2021)

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Biglycan: A regulator of hepatorenal inflammation and autophagy

Martin Schulz et al.

Summary: Soluble biglycan plays a crucial role in inflammation and autophagy, showing diverse functions in inflammatory kidney diseases and chronic liver diseases. Hepatorenal dysfunction is a common complication in patients with cirrhosis, where soluble biglycan may play a key role.

MATRIX BIOLOGY (2021)

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Review Pharmacology & Pharmacy

Transglutaminase 2 as a novel target in chronic kidney disease-Methods, mechanisms and pharmacological inhibition

Judit Prat-Duran et al.

Summary: Chronic kidney disease is a global health problem affecting 10-15% of the population. Transglutaminase 2 (TG2), a multifunctional enzyme, plays a crucial role in renal fibrosis and pharmacological inhibition of TG2 shows antifibrotic effects in CKD. Further research is needed to translate TG2 inhibition into effective treatments for patients with CKD.

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Review Cell & Tissue Engineering

Extracellular matrix extraction techniques and applications in biomedical engineering

Kirthanashri S. Vasanthan et al.

Summary: Tissue engineering involves regeneration and repair of damaged tissue and organs using combinations of cells, growth factors, and scaffolds. Decellularization techniques provide decellularized scaffolds that mimic the in vivo topography for in vitro organ regeneration. The detailed assessment of decellularized extracellular matrix (dECM) offers information on microarchitecture, ECM proteins, biocompatibility, and cell proliferation, with applications in scaffolds, drug delivery, and regeneration.

REGENERATIVE MEDICINE (2021)

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Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse

Long T. Nguyen et al.

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SCIENTIFIC REPORTS (2021)

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CELLS (2021)

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Review Cell Biology

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Matthew Kang et al.

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Fibrillin-1-enriched microenvironment drives endothelial injury and vascular rarefaction in chronic kidney disease

Li Li et al.

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Decoding myofibroblast origins in human kidney fibrosis

Christoph Kuppe et al.

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NATURE (2021)

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Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression

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AMERICAN JOURNAL OF KIDNEY DISEASES (2020)

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Tenascin-C promotes acute kidney injury to chronic kidney disease progression by impairing tubular integrity via αvβ6 integrin signaling.

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KIDNEY INTERNATIONAL (2020)

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Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury

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JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Tenascin-C protects against acute kidney injury by recruiting Wnt ligands

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Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney Fibrosis

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Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis

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NFκB-Induced Periostin ctivates Integrin-β3 Signaling to Promote Renal Injury in GN

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Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis

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Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6

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Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions

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Toll-like Receptor 4 Deficiency Reduces Oxidative Stress and Macrophage Mediated Inflammation in Hypertensive Kidney

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Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD Progression

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RENAL FIBROSIS IN 2015 Understanding the mechanisms of kidney fibrosis

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Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy

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YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis

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Wnt/β-catenin signalling and podocyte dysfunction in proteinuric kidney disease

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Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD

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Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications in ApoE-/- Mice

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TLR4 mutant mice are protected from renal fibrosis and chronic kidney disease progression

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Syndecan-4 Knockout Leads to Reduced Extracellular Transglutaminase-2 and Protects against Tubulointerstitial Fibrosis

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Sonic Hedgehog Is a Novel Tubule-Derived Growth Factor for Interstitial Fibroblasts after Kidney Injury

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Inhibition of Periostin Expression Protects against the Development of Renal Inflammation and Fibrosis

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Biglycan-triggered TLR-2-and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury

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TLR4 Activation Promotes Podocyte Injury and Interstitial Fibrosis in Diabetic Nephropathy

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Syndecans as modulators and potential pharmacological targets in cancer progression

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Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs

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Tenascin C Promiscuously Binds Growth Factors via Its Fifth Fibronectin Type III-Like Domain

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LRP-6 is a coreceptor for multiple fibrogenic signaling pathways in pericytes and myofibroblasts that are inhibited by DKK-1

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Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy

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Toll-Like Receptor 4 Promotes Tubular Inflammation in Diabetic Nephropathy

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Thrombospondin-1 Short Hairpin RNA Suppresses Tubulointerstitial Fibrosis in the Kidney of Ureteral Obstruction by Ameliorating Peritubular Capillary Injury

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Increased Renal Versican Expression Is Associated with Progression of Chronic Kidney Disease

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Matrix metalloproteinases in kidney homeostasis and diseases

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AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY (2012)

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TB domain proteins: evolutionary insights into the multifaceted roles of fibrillins and LTBPs

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BIOCHEMICAL JOURNAL (2011)

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Cellular and molecular mechanisms of renal fibrosis

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Modulation of canonical Wnt signaling by the extracellular matrix component biglycan

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

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Role of Vascular Endothelial Growth Factor in Kidney Disease

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CURRENT VASCULAR PHARMACOLOGY (2010)

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Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation

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New Insights into Epithelial-Mesenchymal Transition in Kidney Fibrosis

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Defining the Role of Integrin αvβ6 in Cancer

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CURRENT DRUG TARGETS (2009)

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CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

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JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2009)

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Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease

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NATURE MEDICINE (2009)

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Secreted protein acidic and rich in cysteine deficiency ameliorates renal inflammation and fibrosis in angiotensin hypertension

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The extra domain A of fibronectin stimulates murine mast cells via Toll-like receptor 4

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JOURNAL OF LEUKOCYTE BIOLOGY (2007)

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alpha v beta 6 integrin regulates renal fibrosis and inflammation in Alport mouse

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R-spondin proteins - A novel link to beta-catenin activation

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The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages

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Review Genetics & Heredity

The role of epithelial-to-mesenchymal transition in renal fibrosis

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JOURNAL OF MOLECULAR MEDICINE-JMM (2004)

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