Inhibition of Protein Arginine Methyltransferase 5 attenuates Dialysis-Related Peritoneal Fibrosis via Suppression of Angiogenesis and Inflammatory State.

Authors

Jinqing Li, Yingfeng Shi, Hui Chen, Daofang Jiang, Xiaoyan Ma, Xialin Li, Peixin Wang, Jiayu Zhu, Qingyi Mo, Shougang Zhuang, Na Liu

Published in

Clinical science (London, England : 1979). Aug 06, 2026. Epub Aug 06, 2026.

Abstract

Dialysis-related peritoneal fibrosis (PF) is a complication of peritoneal dialysis (PD) that leads to ultrafiltration failure and poor technique survival. Currently, no effective therapeutic strategies are available for PF. Protein Arginine Methyltransferase 5 (PRMT5), a major epigenetic regulator catalyzing symmetric dimethylation of arginine residues, has been implicated in fibrotic disorders. However, its role in PD-related PF remains entirely unexplored. In this study, we demonstrate aberrant PRMT5 overexpression in peritoneal samples from PD patients with ultrafiltration failure as well as in murine PF models, in which PRMT5 colocalized with activated fibroblasts and α-SMA-positive myofibroblasts. To further elucidate the specific role of PRMT5, we generated fibroblast-specific PRMT5 knockout mice and established two murine PF models that recapitulate the clinical phenotype. Genetic PRMT5 inhibition attenuated histopathological damage, extracellular matrix (ECM) deposition, angiogenesis and inflammatory infiltration induced by high-glucose PD fluid or chlorhexidine gluconate (CG), thereby improving peritoneal transport function. In vitro, we found genetic PRMT5 inhibition mitigated high-glucose-induced mesothelial-to-mesenchymal transition (MMT) and inflammatory cytokine secretion. Furthermore, pharmacological inhibition of PRMT5 using selective PRMT5 inhibitor EPZ015666 also exhibited therapeutic efficacy in vivo. Mechanistically, our data implicates a PRMT5 mediated inflammation-angiogenesis axis in PF progression. Collectively, our findings establish PRMT5 as a pivotal, druggable epigenetic regulator in dialysis-related PF and provide a compelling rationale for clinical development of PRMT5-targeted strategies to prevent PF.

PMID:
42560699
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.