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MEF2A nuclear translocation mediated by ROCK phosphorylation promotes EZH2 expression and peritoneal fibrosis

Year: 2026

Type: article

Abstract: Prolonged peritoneal dialysis (PD) frequently leads to peritoneal fibrosis (PF). This study aimed to define the role of the Rho-associated coiled-coil containing protein kinase (ROCK) signaling pathway and its downstream effectors, MEF2A and EZH2, in PF. In vivo, a rat PD model was treated with the ROCK inhibitor fasudil or adeno-associated virus-mediated MEF2A knockdown. In vitro, high glucose-stimulated human peritoneal mesothelial cells (HPMCs) were subjected to MEF2A knockdown, EZH2 overexpression, or fasudil treatment. Exposure of HPMCs to high glucose markedly upregulated total and phosphorylated MEF2A (p-MEF2A) and promoted its nuclear translocation. MEF2A knockdown suppressed high glucose-induced upregulation of EZH2 and epithelial-mesenchymal transition (EMT), whereas EZH2 overexpression reversed this protective effect. Dual-luciferase reporter and ChIP-qPCR assays confirmed that MEF2A binds to the EZH2 promoter and activates its transcription. Inhibition of the ROCK pathway with fasudil reversed the high glucose-induced upregulation of MEF2A and suppressed its phosphorylation and nuclear translocation. In vivo, MEF2A knockdown alleviated PF in rats undergoing to long-term PD. Consistently, oral fasudil treatment inhibited the dialysis-induced upregulation of MEF2A and EMT markers. These results reveal a novel ROCK/MEF2A/EZH2 axis in PF pathogenesis, highlighting MEF2A as a potential therapeutic target.

Source: Renal Failure

DOI: 10.1080/0886022x.2026.2664318

Authors: Dandan Chen, Zhikang Sun, Ying Xu, Qinglian Wang

Institutions: Xiangya Hospital Central South University, Shandong Provincial Hospital, Shandong First Medical University

Language: English

Topic: Dialysis and Renal Disease Management

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,306