Non-steroidal mineralocorticoid receptor antagonist finerenone inhibits peritoneal fibrosis induced by high-glucose dialysate via regulating enhancer of zeste homolog 2 (EZH2) expression

非甾体类盐皮质激素受体拮抗剂非奈利酮通过调节增强子Zeste同源物2 (EZH2) 的表达来抑制高糖透析液诱导的腹膜纤维化。

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Abstract

Finerenone, a novel high-selective aldosterone receptor antagonist, exhibits powerful anti-inflammatory and antifibrotic effects in previous researches. The aim of our study was to investigate of it on peritoneal fibrosis. In our current research, we found that high glucose could induce epithelial mesothelial transformation (EMT) of peritoneal mesothelial cells (HPMCs). Under high glucose stimulation, the addition of finerenone could alleviate high glucose induced EMT and disordered cytoskeleton rearrangement in HPMCs. Moreover, finerenone decreased the expression of enhancer of zeste homolog 2 (EZH2). Results of rescue experiment showed that after overexpression of EZH2 in the presence of finerenone, the protective effect of finerenone on EMT, migration capacity and cytoskeleton rearrangement was counteracted by EZH2 overexpression. The above results have also been demonstrated in in vivo experiments. These findings imply that finerenone could alleviate EMT and peritoneal fibrosis via regulating EZH2. More studies are needed to validate it and explore further mechanism.

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