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Versican regulating viscoelasticity drives pleural fibrosis via mechanotransductive signaling

ABSTRACT: Extracellular matrix (ECM) disorder was considered as the result of fibrosis, but it is recently recognized that fibrotic ECM activates a profibrotic positive feedback loop and contributes to development of fibrosis. Versican, an ECM component, participates in cell-ECM interaction and ECM regeneration. In pleura, versican is primarily derived from pleural mesothelial cells (PMCs). However, little was known about the role and mechanism of versican in pleural fibrosis. In this study, versican and versican-mediated pleural viscoelasticity was found elevated in both human and murine pleural fibrotic tissues. Versican knockdown by shRNA prevented increases of viscoelasticity as well as pleural fibrosis. High level of versican and viscoelasticity promoted mesothelial to mesenchymal transition (MesoMT) in PMCs. Mechanistically, increased viscoelasticity induced pleural fibrosis through CD44/USP10/Smad4 mechanotransduction pathway. In conclusion, these results revealed that excessive versican in fibrotic pleural ECM enhanced ECM viscoelasticity, and consequently promoted progression of pleural fibrosis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Wanli Ma

PROVIDER: PXD073100 | iProX | Thu Jan 15 00:00:00 GMT 2026

REPOSITORIES: iProX

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