Splicing factor SRSF6 mediates pleural fibrosis

• DOI: 10.1172/jci.insight.146197
• Publication Date: 2021-04-27T20:34:49Z
• Authors: Li-Mei Liang; Liang Xiong; Pei-Pei Cheng; Shuai-Jun Chen; Xiao Feng; Ya-Ya Zhou; Qian Niu; Meng Wang; Qianlan Chen; Lin-Jie Song; Fan Yu; Xin-Liang He; Fei Xiang; Xiaorong Wang; Hong Ye; Wan-Li Ma
• Keywords: Male; 0301 basic medicine; Pulmonology; Serine-Arginine Splicing Factors; R; Pleural Diseases; Phosphoproteins; Fibrosis; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Medicine; Animals; Humans; Pleura; Research Article; Signal Transduction

Pleural fibrosis is defined as an excessive deposition of extracellular matrix that results in destruction the normal pleural tissue architecture and compromised function. Tuberculous pleurisy, asbestos injury, rheumatoid pleurisy are main causes fibrosis. mesothelial cells (PMCs) play a key role However, detailed mechanisms poorly understood. Serine/arginine-rich protein SRSF6 belongs to family highly conserved RNA-binding splicing-factor proteins. Based on its known functions, should be expected fibrotic diseases. remains unknown. In this study, was found increased tuberculous effusions (TBPE) from patients, decellularized TBPE, bleomycin, TGF-β1 were confirmed increase levels PMCs. vitro, mediated PMC proliferation synthesis COL1A2. vivo, inhibition prevented mouse experimental Finally, activated SMAD2/3, SOX4, depressed miRNA-506-3p associated with upregulation These observations support model which induces through cluster pathway, including SRSF6/WNT5A SRSF6/SMAD1/5/9 signaling. conclusion, we propose splicing factor strategy for treatment