Epigallocatechin-3-gallate increases autophagic activity attenuating TGF-β1-induced transformation of human Tenon's fibroblasts

作者：Zhang, Yu Lin; Zhang, Yu Qiao; Lin, Hong Liang; Qin, Yong Jie; Zeng, Jin; Chen, Yan Lei; Niu, Yong Yi; Pang, Chi Pui; Chu, Wai Kit; Zhang, Hong Yang^*

来源：Experimental Eye Research, 2021, 204: 108447.

DOI：10.1016/j.exer.2021.108447

• EGCG
• TGF-?1
• Autophagy
• Human Tenon?s fibroblasts
• Myofibroblast transformation

We previously found that epigallocatechin-3-gallate (EGCG) could inhibit the myofibroblast transformation of human Tenon?s fibroblasts, however, the underlying mechanism remained unclear. We therefore investigated whether the autophagic regulation involved in the anti-fibrotic function of EGCG. The fibroblasts were subjected to transforming growth factor beta-1 (TGF-?1) induction followed by EGCG treatments. The autophagic flux was examined by transmission electron microscopy and autophagic flux analysis. The levels of autophagy-related proteins (LC3? and p62) and alpha-smooth muscle actin (?-SMA) were measured by Western blot and immunofluorescence. Results showed that TGF-?1 partially inhibited the autophagic function of Tenon?s fibroblasts. But this inhibition effect was rescued by LY2157299, a TGF-?R1 selective inhibitor. Compared with the cells treated with TGF-?1 alone, EGCG treatments increased the amount of autophagosomes and autolysosomes, evaluated the ratio of LC3-II to LC3-I and decreased p62 level. Our results indicated that EGCG could recover the activity of autophagy in the TGF-?1-treated cells. Moreover, treatments with EGCG significantly decreased the ?-SMA expression. Taken together, these findings revealed that autophagic regulation involved in the action of EGCG against TGF-?1-induced transformation of Tenon?s fibroblasts. Through increasing intracellular autophagy, EGCG could be a potential anti-fibrotic reagent for preventing subconjunctival fibrosis after glaucoma filtration surgery.

• 单位
  汕头大学; 南方医科大学; 广东省人民医院