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SMYD2 has been shown to act as an oncogene to promote disease progression in a variety of cancer diseases, but its role in chronic kidney diseases (CKD) pathogenesis has not been fully elucidated. This study aims to investigate the effect of SMYD2 on cisplatin\u2010induced CKD and its underlying mechanisms. In this study, we found that cisplatin caused severe renal injury in mice, which was accompanied by the up\u2010regulation of SMYD2 expression. AZ505 treatment significantly down\u2010regulated cisplatin\u2010induced renal injury and fibrosis. It also alleviated renal apoptosis and inhibited the phosphorylation level of NF\u2010\u03baB p65. Conditional knockdown of\n                    <jats:italic>Smyd2<\/jats:italic>\n                    achieved similar effects as AZ505. In renal tubular epithelial cells, inhibition or silencing of SMYD2 down\u2010regulated cisplatin\u2010induced apoptotic response, while overexpression of SMYD2 induced apoptotic response and activated NF\u2010\u03baB in response to the up\u2010regulation of SMYD2 expression. Up\u2010regulation of SMYD2 induced interaction and phosphorylation of SMYD2 and NF\u2010\u03baB p65, and inhibition of NF\u2010\u03baB activation further suppressed cisplatin\u2010induced NF\u2010\u03baB activation and apoptosis. The present study suggests that up\u2010regulation of SMYD2 expression in cisplatin\u2010induced CKD may promote apoptosis of renal tubular epithelial cells and accelerate the process of renal injury through NF\u2010\u03baB activation. SMYD2 may serve as a potential target for effective CKD treatment.\n                  <\/jats:p>","DOI":"10.1096\/fj.202402703r","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T07:10:23Z","timestamp":1747725023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SMYD2 Promotes Renal Tubular Cell Apoptosis and Chronic Kidney Disease Following Cisplatin Nephrotoxicity"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8087-7914","authenticated-orcid":false,"given":"Siyang","family":"Zuo","sequence":"first","affiliation":[{"name":"Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical University  Guiyang China"},{"name":"Guizhou Institute of Precision Medicine Affiliated Hospital of Guizhou Medical University  Guiyang 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