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非甾体类盐皮质激素受体拮抗剂非奈利酮通过调节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。

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

作者信息

Chen Dandan, Shu Jianqiang, Zhang Xinyu, Wang Simeng, Sun Jingshu, Chong Nannan, Sun Zhikang, Xu Ying, Wang Qinglian

机构信息

Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.

Weifang People's Hospital, Weifang, Shandong, China.

出版信息

Ren Fail. 2025 Dec;47(1):2491156. doi: 10.1080/0886022X.2025.2491156. Epub 2025 May 13.

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 experiments. These findings imply that finerenone could alleviate EMT and peritoneal fibrosis regulating EZH2. More studies are needed to validate it and explore further mechanism.

摘要

非奈利酮是一种新型高选择性醛固酮受体拮抗剂,在以往研究中显示出强大的抗炎和抗纤维化作用。我们研究的目的是探讨其对腹膜纤维化的影响。在我们目前的研究中,我们发现高糖可诱导腹膜间皮细胞(HPMC)发生上皮-间皮转化(EMT)。在高糖刺激下,添加非奈利酮可减轻高糖诱导的HPMC的EMT和细胞骨架重排紊乱。此外,非奈利酮降低了zeste同源物2增强子(EZH2)的表达。挽救实验结果表明,在存在非奈利酮的情况下过表达EZH2后,EZH2的过表达抵消了非奈利酮对EMT、迁移能力和细胞骨架重排的保护作用。上述结果也在实验中得到了证实。这些发现表明,非奈利酮可通过调节EZH2减轻EMT和腹膜纤维化。需要更多的研究来验证这一点并进一步探索其机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd21/12082730/97371eb1e024/IRNF_A_2491156_F0001_C.jpg

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