Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways
Objective. Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. Methods. Mouse models of hepatic fibrosis were established by intraperit...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/6175091 |
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| _version_ | 1832562259695501312 |
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| author | Ning Liu Jiao Feng Xiya Lu Zhilu Yao Qing Liu Yang Lv Yuru Han Jingfan Deng Yingqun Zhou |
| author_facet | Ning Liu Jiao Feng Xiya Lu Zhilu Yao Qing Liu Yang Lv Yuru Han Jingfan Deng Yingqun Zhou |
| author_sort | Ning Liu |
| collection | DOAJ |
| description | Objective. Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. Methods. Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl4) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl4 model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results. Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor β1 (TGF-β1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Conclusion. Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-β1-mediated Smad3 and p38 MAPK signaling pathways. |
| format | Article |
| id | doaj-art-3b8d30ffb99145eebe4c9b7161c89afe |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3b8d30ffb99145eebe4c9b7161c89afe2025-02-03T01:23:01ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/61750916175091Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK PathwaysNing Liu0Jiao Feng1Xiya Lu2Zhilu Yao3Qing Liu4Yang Lv5Yuru Han6Jingfan Deng7Yingqun Zhou8Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, ChinaObjective. Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. Methods. Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl4) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl4 model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results. Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor β1 (TGF-β1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Conclusion. Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-β1-mediated Smad3 and p38 MAPK signaling pathways.http://dx.doi.org/10.1155/2019/6175091 |
| spellingShingle | Ning Liu Jiao Feng Xiya Lu Zhilu Yao Qing Liu Yang Lv Yuru Han Jingfan Deng Yingqun Zhou Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways Mediators of Inflammation |
| title | Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways |
| title_full | Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways |
| title_fullStr | Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways |
| title_full_unstemmed | Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways |
| title_short | Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways |
| title_sort | isorhamnetin inhibits liver fibrosis by reducing autophagy and inhibiting extracellular matrix formation via the tgf β1 smad3 and tgf β1 p38 mapk pathways |
| url | http://dx.doi.org/10.1155/2019/6175091 |
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