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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 the present 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 \u03b1-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 deposition, angiogenesis, and inflammatory infiltration induced by high-glucose PD fluid or chlorhexidine gluconate, thereby improving peritoneal transport function. In vitro, we found genetic PRMT5 inhibition mitigated high-glucose-induced mesothelial-to-mesenchymal transition and inflammatory cytokine secretion. Furthermore, pharmacological inhibition of PRMT5 using selective PRMT5 inhibitor EPZ015666 also exhibited therapeutic efficacy in vivo. Mechanistically, our data implicate 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.<\/jats:p>","DOI":"10.1042\/cs20250416","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:29:06Z","timestamp":1786030146000},"page":"1873-1893","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of protein arginine methyltransferase 5 attenuates dialysis-related peritoneal fibrosis via suppression of angiogenesis and inflammatory state"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-392X","authenticated-orcid":false,"given":"Jinqing","family":"Li","sequence":"first","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfeng","family":"Shi","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daofang","family":"Jiang","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Ma","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xialin","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Zhu","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyi","family":"Mo","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shougang","family":"Zhuang","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"},{"name":"2Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, RI, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-8209","authenticated-orcid":false,"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"1Department of Nephrology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"2026082005165449600_B1","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/s41581-022-00623-7","article-title":"Epidemiology of peritoneal dialysis outcomes","volume":"18","author":"Bello","year":"2022","journal-title":"Nat. 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