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Contribution of keratinocytes to dermal fibrosis

CURRENT OPINION IN RHEUMATOLOGY (2022)

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Article Allergy

Current Concepts on the Pathogenesis of Systemic Sclerosis

Marie Elise Truchetet et al.

Summary: Systemic sclerosis (SSc) is a disease characterized by skin and internal organ fibrosis, vascular modifications, and autoimmunity. It predominantly affects women and has heterogeneous clinical presentations and courses. The pathogenesis involves genetic predisposition, environmental factors, and epigenetic modifications that lead to immune-inflammatory dysregulation and abnormal cell behavior. Myofibroblasts play a crucial role in the disease by promoting fibrosis and matrix deposition. Other cell types, such as pericytes, platelets, and keratinocytes, are also involved. T cell subsets and autoantibodies contribute to fibroblast and endothelial cell dysfunction. Recent studies have revealed heterogeneity in SSc cell differentiation and functional states. Understanding the heterogeneity and pathogenic mechanisms will aid in developing personalized therapeutic approaches.

CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY (2023)

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Article Genetics & Heredity

Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar

Shunuo Zhang et al.

Summary: In this study, the biological characteristics during Hypertrophic scar (HS) formation were investigated through the integrative analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data. The study revealed that FB-1 fibroblasts were significantly expanded in HS, while the proportion of KC-2 keratinocytes was reduced. Cell-cell communication analysis showed changes in the autocrine signaling of HB-1 and the intercellular contacts between FB-1/FB-5 and KC-2 in HS. The transcriptionally regulatory network involved CREB3L1 and TWIST2 as critical transcription factors in myofibroblast formation in HS.

FRONTIERS IN GENETICS (2022)

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Review Genetics & Heredity

Human organs-on-chips for disease modelling, drug development and personalized medicine

Donald E. Ingber

Summary: This Review discusses the types of single and multiple human organ-on-a-chip (organ chip) microfluidic devices and their diverse applications for disease modeling, drug development, and personalized medicine. It also addresses the challenges that must be overcome for organ chips to reach their full potential and discusses recent advances in the field.

NATURE REVIEWS GENETICS (2022)

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Article Rheumatology

Self-Assembled Human Skin Equivalents Model Macrophage Activation of Cutaneous Fibrogenesis in Systemic Sclerosis

Mengqi Huang et al.

Summary: This study developed and tested a self-assembled skin equivalent (saSE) system that mimics the cross-talk between macrophages and fibroblasts in systemic sclerosis (SSc). The researchers found that reciprocal activation between macrophages and fibroblasts increases tissue thickness and stiffness, which is partly dependent on TGF-β activation.

ARTHRITIS & RHEUMATOLOGY (2022)

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Article Rheumatology

Association of differentially expressed genes and autoantibody type in patients with systemic sclerosis

Jun Inamo

Summary: This study investigated the relationship between different types of autoantibodies and gene expression profiles in skin lesions of patients with Systemic Sclerosis (SSc), identifying specific dysregulated pathways associated with each autoantibody type. By analyzing gene expression data, the study revealed potential new therapeutic targets for SSc based on specific autoantibody profiles.

RHEUMATOLOGY (2021)

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Article Rheumatology

Dysfunctional Keratinocytes Increase Dermal Inflammation in Systemic Sclerosis: Results From Studies Using Tissue-Engineered Scleroderma Epidermis

Barbara Russo et al.

Summary: Objective evidence suggests that keratinocyte-fibroblast interactions are abnormal in systemic sclerosis (SSc). This study found that SSc epidermal equivalents (EEs) exhibited aberrant differentiation and enhanced expression of activation markers, replicating the abnormalities seen in SSc epidermis. The dysregulation of genes from the homeobox family and increased metabolic and oxidative stress in SSc EEs may contribute to chronic inflammation and dermal fibrosis.

ARTHRITIS & RHEUMATOLOGY (2021)

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Article Dermatology

IFN-γ-Stimulated Apoptotic Keratinocytes Promote Sclerodermatous Changes in Chronic Graft-Versus-Host Disease

Akimasa Saito et al.

Summary: In patients with GVHD, KCs in skin lesions of chronic GVHD show marked production of TGF beta 1, while IFN-gamma-deficient CD8 T-cell recipients have lower expression of TGF beta 1 in the epidermis. IFN-gamma promotes TGF beta 1 production by apoptotic KCs, mediating the development of widespread sclerodermatous changes in KC-targeting GVHD.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2021)

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Review Materials Science, Biomaterials

Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development

Andrea De Pieri et al.

Summary: Systemic sclerosis is a complex multisystem disease with no curative therapy. Advanced in vitro models mimic critical aspects of the pathology and are valuable for investigating novel pharmaceutical therapies.

ADVANCED BIOLOGY (2021)

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Article Biochemical Research Methods

Protocol for in vitro skin fibrosis model to screen the biological effects of antifibrotic compounds

Amir M. Alsharabasy et al.

Summary: This report presents a reproducible protocol for producing a skin fibrosis model using human dermal fibroblasts seeded in collagen hydrogel. Detailed procedures for the fabrication of cell/hydrogel constructs, fibrosis induction, and protein extraction for western blotting analysis are provided, along with how this model can be used to investigate the anti-fibrotic functions of certain chemical compounds.

STAR PROTOCOLS (2021)

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Article Dermatology

IL-17A Dissociates Inflammation from Fibrogenesis in Systemic Sclerosis

Aleksandra Maria Dufour et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2020)

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Article Rheumatology

Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile

Brian Skaug et al.

ANNALS OF THE RHEUMATIC DISEASES (2020)

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Article Rheumatology

Systemic Sclerosis Dermal Fibroblasts Induce Cutaneous Fibrosis Through Lysyl Oxidase-like 4: New Evidence From Three-Dimensional Skin-like Tissues

Mengqi Huang et al.

ARTHRITIS & RHEUMATOLOGY (2020)

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Review Immunology

Interplay Between Keratinocytes and Fibroblasts: A Systematic Review Providing a New Angle for Understanding Skin Fibrotic Disorders

Barbara Russo et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Immunology

A Method for Isolating and Culturing Skin Cells: Application to Endothelial Cells, Fibroblasts, Keratinocytes, and Melanocytes From Punch Biopsies in Systemic Sclerosis Skin

Pauline Henrot et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Rheumatology

Vascularised human skin equivalents as a novel in vitro model of skin fibrosis and platform for testing of antifibrotic drugs

Alexandru-Emil Matei et al.

ANNALS OF THE RHEUMATIC DISEASES (2019)

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Article Cell Biology

Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule

Preethi Vijayaraj et al.

CELL REPORTS (2019)

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Article Immunology

Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma

Takehiro Takahashi et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2017)

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Article Rheumatology

Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta

Sara S. McCoy et al.

RHEUMATOLOGY (2017)

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Article Immunology

EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin

Hideo Kudo et al.

JOURNAL OF IMMUNOLOGY (2015)

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Article Biochemical Research Methods

Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms

J. Matthew Mahoney et al.

PLOS COMPUTATIONAL BIOLOGY (2015)

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Article Dermatology

Abnormally Differentiating Keratinocytes in the Epidermis of Systemic Sclerosis Patients Show Enhanced Secretion of CCN2 and S100A9

Joanna Nikitorowicz-Buniak et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2014)

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Article Dermatology

Increased KGF Expression Promotes Fibroblast Activation in a Double Paracrine Manner Resulting in Cutaneous Fibrosis

Johanna Canady et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2013)

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Article Dermatology

Epithelial Cells Promote Fibroblast Activation via IL-1α in Systemic Sclerosis

Nima Aden et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2010)

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Article Dermatology

Inhibition of dermal fibrosis in self-assembled skin equivalents by undifferentiated keratinocytes

Xinwen Wang et al.

JOURNAL OF DERMATOLOGICAL SCIENCE (2009)

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