Versican regulating viscoelasticity drives pleural fibrosis via mechanotransductive signaling.

作者：Zi-Heng Jia, Xin-Liang He, Xiao-Lin Cui, Qi Li, Pei-Pei Cheng, Zhao Li-qin, Shu-Yi Ye, Shi-He Hu, Chen-Yue Lian, He-De Zhang, Li-Mei Liang, Lin-Jie Song, F Yu, Liang Xiong, Fei Xiang, Xiaorong Wang, Meng Wang, Xiyong Dai, Hong Ye, Wan-Li Ma · 发表于：PubMed · 年份：2026 · DOI：10.1172/jci.insight.199507 · 研究领域：Proteoglycans and glycosaminoglycans research、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Pleural and Pulmonary Diseases

Extracellular matrix (ECM) disorder was believed to result from fibrosis, but it has recently been recognized that fibrotic ECM initiates a self-reinforcing circuit and contributes to the 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, the role and mechanism of versican in pleural fibrosis has remained unknown. In this study, versican and versican-mediated pleural viscoelasticity were found to be elevated in both human and murine pleural fibrotic tissues. Versican knockdown by shRNA prevented increases in viscoelasticity as well as pleural fibrosis. High levels of versican and viscoelasticity promoted mesothelial-mesenchymal transition in PMCs. Mechanistically, increased viscoelasticity induced pleural fibrosis through the 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.