Regulation of transforming growth factor β-mediated epithelial-mesenchymal transition of lens epithelial cells by c-Src kinase under high glucose conditions.

Abstract

Recent studies have reported that high glucose (HG) conditions may contribute to the acceleration of renal cell apoptosis and renal fibrosis by inducing epithelial-mesenchymal transition (EMT) of tubular epithelial cells, in which c-Src kinase and transforming growth factor (TGF)-β are key modulators. In the present study, the roles of c-Src kinase and TGF-β in EMT of lens epithelial cells (LECs) under HG conditions were investigated. Results indicated human lens epithelial B3 (HLE-B3) cells under HG conditions exhibited significantly increased protein expression levels of phosphorylated c-Src (p-Src418) (P<0.05) and secreted a significantly increased amount of TGF-β compared with HLE-B3 cells under normal glucose conditions (P<0.05). Notably the c-Src inhibitor PP1 and the activin receptor-like kinase 5 (ALK5) inhibitor SB431542 suppressed EMT of HLE-B3 cells. Results indicated that PP1 significantly inhibited the activities of c-Src and ALK5 and the secretion of TGF-β, whereas SB431542 only significantly downregulated the protein expression levels and secretion of TGF-β (P<0.05). Following c-Src knockdown, the protein expression levels of p-Src418, ALK5 and TGF-β were significantly decreased, the secretion of TGF-β was significantly suppressed (both P<0.05) and EMT was decreased in HLE-B3 cells. These results suggest that c-Src and TGF-β may promote EMT of LECs under HG conditions, with c-Src as the upstream regulatory molecule. Thus, the signal axis of c-Src/TGF-β in EMT of LECs may be a potential novel therapeutic target for the prevention of diabetic subcapsular cataract.

• Authors: Zhi-Hua Han, Fang Wang, Fu-Lei Wang, Qi Liu, Jian Zhou
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 16 Issue 2 Pg. 1520-1528 (Aug 2018) ISSN: 1792-0981 [Print] Greece
• PMID: 30116401 (Publication Type: Journal Article)