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Its effect on peritoneal fibrosis remains unexplored. In this study, we investigated its effects on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG) in a murine model. We found that SMYD2 and trimethylated histone substrate H3K36 (H3K36me3) were highly expressed in the peritoneal tissue following CG injection, and administration of AZ505 remarkably inhibited their expression, along with attenuating CG\u2013induced peritoneal fibrosis and expression of collagen I and fibronectin. Moreover, AZ505 also significantly reduced expression of CD31 (marker of angiogenesis) and CD68\u2010positive macrophage infiltration in the CG\u2010injured peritoneum. AZ505 further inhibited CG\u2010induced epithelial\u2010to\u2010mesenchymal transition (EMT) of peritoneal mesothelial cells, manifested by decreasing expression of \u03b1\u2010smooth muscle antigen (\u03b1\u2010SMA) and Vimentin and restoring E\u2010cadherin expression, accompanied by suppressing expression of two transcription factors, Snail and Twist. Finally, AZ505 inhibited CG\u2010induced phosphorylation of AKT and increased expression of phosphatase and tensin (PTEN), a key phosphatase. These data suggest that AZ505 may protect against peritoneal fibrosis by inhibiting EMT, inflammation and angiogenesis, due to its blockade of methylation modification catalysed by SMYD2.<\/jats:p>","DOI":"10.1111\/1440-1681.70035","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T22:00:47Z","timestamp":1748210447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Inhibitor of Methyltransferase\n                    <scp>SMYD2<\/scp>\n                    ,\n                    <scp>AZ505<\/scp>\n                    Protects Against Peritoneal Fibrosis in Mice"],"prefix":"10.1111","volume":"52","author":[{"given":"Taijing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Nephrology Affiliated Huishan Hospital of Xinglin College, Nantong University  Wuxi 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