Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation
Abstract Hepatic steatosis, inflammation, and fibrosis are the hallmarks of metabolic‐associated steatohepatitis (MASH), a serious health risk. This study emphasizes how important gelsolin (GSN) is to the pathophysiology of MASH. The results show that GSN is significantly overexpressed in both MASH...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202416489 |
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| author | Yiwei Lu Tong Ji Zhichao Ye Jianing Yan Chao Wang Jiachen Chen Ziyang Jin Yongji Zhu Xiujun Cai Yifan Wang |
| author_facet | Yiwei Lu Tong Ji Zhichao Ye Jianing Yan Chao Wang Jiachen Chen Ziyang Jin Yongji Zhu Xiujun Cai Yifan Wang |
| author_sort | Yiwei Lu |
| collection | DOAJ |
| description | Abstract Hepatic steatosis, inflammation, and fibrosis are the hallmarks of metabolic‐associated steatohepatitis (MASH), a serious health risk. 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, Gsn knockout (KO) (Gsn−/−) mice demonstrate exacerbated hepatic steatosis, inflammation, and fibrosis, underscoring GSN's protective function. Remarkably, adeno‐associated virus (AAV)‐mediated restoration of Gsn substantially alleviates these pathological features, indicating its therapeutic potential. Mechanistically, the absence of GSN leads to increased F‐actin polymerization and heightened activation of Yes‐associated protein (YAP), thereby intensifying the inflammatory response. Subsequently, the experimental data identify a co‐expression 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‐mediated 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. |
| format | Article |
| id | doaj-art-324c794fe42543b4866571d1faa4e790 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-324c794fe42543b4866571d1faa4e7902025-08-20T03:22:15ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.202416489Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 DegradationYiwei Lu0Tong Ji1Zhichao Ye2Jianing Yan3Chao Wang4Jiachen Chen5Ziyang Jin6Yongji Zhu7Xiujun Cai8Yifan Wang9Department of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaDepartment of General Surgery Sir Run Run Shaw Hospital Affiliated to School of Medicine Zhejiang University Hangzhou 310016 ChinaAbstract Hepatic steatosis, inflammation, and fibrosis are the hallmarks of metabolic‐associated steatohepatitis (MASH), a serious health risk. 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, Gsn knockout (KO) (Gsn−/−) mice demonstrate exacerbated hepatic steatosis, inflammation, and fibrosis, underscoring GSN's protective function. Remarkably, adeno‐associated virus (AAV)‐mediated restoration of Gsn substantially alleviates these pathological features, indicating its therapeutic potential. Mechanistically, the absence of GSN leads to increased F‐actin polymerization and heightened activation of Yes‐associated protein (YAP), thereby intensifying the inflammatory response. Subsequently, the experimental data identify a co‐expression 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‐mediated 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.https://doi.org/10.1002/advs.202416489F‐actingelsolin (GSN)metabolic‐associated steatohepatitis (MASH)P53YAP |
| spellingShingle | Yiwei Lu Tong Ji Zhichao Ye Jianing Yan Chao Wang Jiachen Chen Ziyang Jin Yongji Zhu Xiujun Cai Yifan Wang Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation Advanced Science F‐actin gelsolin (GSN) metabolic‐associated steatohepatitis (MASH) P53 YAP |
| title | Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation |
| title_full | Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation |
| title_fullStr | Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation |
| title_full_unstemmed | Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation |
| title_short | Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation |
| title_sort | gelsolin s protective role in mash through f actin regulation and p53 degradation |
| topic | F‐actin gelsolin (GSN) metabolic‐associated steatohepatitis (MASH) P53 YAP |
| url | https://doi.org/10.1002/advs.202416489 |
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