Authors
Laura Muraine, Mona Bensalah, Stephen Gargan, Paul Dowling, Anne Bigot, Valérie Allamand, Jamila Dhiab, Maria Kondili, Sophie Perié, Jean Lacau St-Guily, Gillian Butler-oBrowne, Vincent Mouly, Kay Ohlendieck, Capucine Trollet, Elisa Negroni
Published in
EMBO reports. Jun 19, 2026. Epub Jun 19, 2026.
Abstract
Muscle fibrosis is a major driver of progression in diverse myopathies, yet the conserved molecular mediators of this process in humans remain poorly defined. Here, we identify collagen VI as a common regeneration-impairing extracellular matrix (ECM) component across three distinct human myopathies: Duchenne Muscular Dystrophy (DMD), Oculopharyngeal Muscular Dystrophy (OPMD), and Inclusion Body Myositis (IBM). Proteomic profiling of fibrotic biopsies reveals consistent upregulation of collagen VI and laminin γ1, alongside disease-specific alterations. Fibroadipogenic progenitors (FAPs) are the predominant source of these ECM components, including collagen VI and laminin γ1. Functionally, xenotransplantation of patient-derived FAPs into regenerating mouse muscle induces localized collagen deposition, myofiber atrophy, and depletion of Pax7⁺ muscle stem cells. Mechanistic assays demonstrate that FAP-derived collagen VI is sufficient to impair myogenic fusion, while silencing COL6 in patient FAPs restores fusion capacity, directly linking pathological collagen VI deposition to regeneration failure. Our findings uncover collagen VI as a conserved effector of fibrosis and stem cell niche disruption in human myopathies, positioning it as a potential therapeutic target across genetically and clinically distinct muscle diseases.
PMID:
42321489
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.
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