Abstract
Extracellular matrix (ECM) disorder was considered as the result of fibrosis, but it is recently recognized that fibrotic ECM initiates a self-reinforcing circuit 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, the role and mechanism of versican in pleural fibrosis remained unknown. 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.
Authors
Zi-Heng Jia, Xin-Liang He, Xiao-Lin Cui, Qian Li, Pei-Pei Cheng, Li-Qin Zhao, Shu-Yi Ye, Shi-He Hu, Chen-Yue Lian, He-De Zhang, Li-Mei Liang, Lin-Jie Song, Fan Yu, Liang Xiong, Fei Xiang, Xiaorong Wang, Meng Wang, Xiyong Dai, Hong Ye, Wan-Li Ma
