Study on the Role of FGF9/ERK/MMP9 Pathway in Age‐Related Cataract and in (‐)‐Epigallocatechin‐3‐gallate Protecting Lens Epithelial Cells From Apoptosis
Jiale Yu, Yifan Wu, Jianan Wu, Cuige Shi, Xiaofeng Chen, Ying Wei, Lina Guan, Jialing He, Yue Zhang, Zihan Xiang, Dongmei Su, Shanshan Hu, Xu MaABSTRACT
Age‐related cataract (ARC) is the most prevalent form of cataract. Oxidative stress‐induced apoptosis of lens epithelial cells (LECs) is a major pathogenic factor, but its underlying molecular mechanisms remain incompletely understood. This study investigated the roles of FGF9, ERK , and MMP9 in ARC and examined whether the FGF9 /ERK/ MMP9 pathway is involved in the protective effects of (‐)‐epigallocatechin‐3‐gallate (EGCG) against LEC apoptosis. FGF9 and MMP9 were downregulated at both the mRNA and protein levels in ARC mice and H 2 O 2 (200 µM)‐treated HLE‐B3 cells as determined by immunohistochemistry, Western blotting and qRT‐PCR. FGF9 overexpression increased cell viability and reduced apoptosis in H 2 O 2 ‐treated HLE‐B3 cells, as demonstrated by CCK‐8 and Hoechst 33342 staining. EGCG treatment improved cell viability and increased FGF9 expression in H 2 O 2 ‐treated cells and lens tissues from ARC mice. Conversely, FGF9 knockdown attenuated the protective effect of EGCG. Further experiments suggested that FGF9 may contribute to the anti‐apoptotic effects of EGCG by modulating ERK phosphorylation and MMP9 expression. ERK activation by TBHQ increased the viability of H 2 O 2 ‐treated HLE‐B3 cells, whereas ERK inhibition with PD98059 attenuated the protective effects of EGCG and decreased MMP9 expression. Moreover, MMP9 knockdown increased cleaved caspase‐9 expression and was accompanied by increased apoptosis in LECs. These findings suggest that the FGF9 /ERK/ MMP9 pathway is involved in oxidative stress‐induced LEC apoptosis and may contribute, at least in part, to the protective effects of EGCG in experimental models of ARC.