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This study emphasizes how important gelsolin (GSN) is to the pathophysiology of MASH. The results show that GSN is significantly overexpressed in both MASH patients and animal models. Under MASH models,\n                    <jats:italic>Gsn<\/jats:italic>\n                    knockout (KO) (\n                    <jats:italic>Gsn<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice demonstrate exacerbated hepatic steatosis, inflammation, and fibrosis, underscoring GSN's protective function. Remarkably, adeno\u2010associated virus (AAV)\u2010mediated restoration of\n                    <jats:italic>Gsn<\/jats:italic>\n                    substantially alleviates these pathological features, indicating its therapeutic potential. Mechanistically, the absence of GSN leads to increased F\u2010actin polymerization and heightened activation of Yes\u2010associated protein (YAP), thereby intensifying the inflammatory response. Subsequently, the experimental data identify a co\u2010expression relationship between GSN and MDM2, and GSN is found to facilitate the ubiquitination and subsequent degradation of P53 via MDM2, a crucial process for liver protection. These findings imply that GSN is essential for controlling important molecular pathways in MASH by encouraging P53's MDM2\u2010mediated degradation, which lessens the severity of hepatic steatosis. The research offers important new understandings of the molecular mechanisms of MASH and suggests GSN as a viable therapeutic target to reduce liver damage and preserve hepatic homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202416489","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:41:31Z","timestamp":1747723291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gelsolin's Protective Role in MASH through F\u2010Actin Regulation and P53 Degradation"],"prefix":"10.1002","volume":"12","author":[{"given":"Yiwei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University  Hangzhou 310016 China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments  Hangzhou 310016 China"},{"name":"Zhejiang 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