β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models
Background The restoration of the Wnt/β-catenin pathway to alleviate alcoholic fatty liver disease (AFLD) progression is under study as a new strategy for alcoholic liver disease (ALD) treatment. Recent studies have indicated that interferon-stimulated gene 15 (ISG15) can covalently bind to β-cateni...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Redox Report |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2022.2109360 |
| _version_ | 1811237613580845056 |
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| author | Qi Ding Guodong Zhang Yang Wang Lei Xu Meifei Wu Yiwen Zhou Tao Xu Xiaoming Meng Cheng Huang Lei Zhang |
| author_facet | Qi Ding Guodong Zhang Yang Wang Lei Xu Meifei Wu Yiwen Zhou Tao Xu Xiaoming Meng Cheng Huang Lei Zhang |
| author_sort | Qi Ding |
| collection | DOAJ |
| description | Background The restoration of the Wnt/β-catenin pathway to alleviate alcoholic fatty liver disease (AFLD) progression is under study as a new strategy for alcoholic liver disease (ALD) treatment. Recent studies have indicated that interferon-stimulated gene 15 (ISG15) can covalently bind to β-catenin by HECT E3 ubiquitin ligase 5 (HERC5), leading to ISG degradation and downregulation of β-catenin levels. However, the relationship between β-catenin and the ISG15 system in AFLD remains unclear.Methods Here, we explored the roles of the ISG15 system in β-catenin activation and in the pathogenesis of alcohol-induced liver injury and steatosis.Results In this study, HERC5 silencing upregulated β-catenin protein expression and inhibited lipid metabolism disorders and cell apoptosis. Reduced β-catenin protein expression, increased lipid metabolism disorders, and cell apoptosis were detected in cells induced with HERC5 overexpression, which was reversible with the reactive oxygen species (ROS) inhibitor. All the above results were statistically analyzed. Thus, these observations demonstrate that β-catenin ISGylation is a prominent regulator of ALD pathology, which works by regulating ROS to induce lipid metabolism disorders and cell apoptosis.Conclusion Our findings provided the mechanism involved in the β-catenin ISGylation, allowing for future studies on the prevention or amelioration of liver injury in ALD. |
| first_indexed | 2024-04-12T12:26:19Z |
| format | Article |
| id | doaj.art-76b1d8dc651e4e43a9fbf45be9ee8eba |
| institution | Directory Open Access Journal |
| issn | 1351-0002 1743-2928 |
| language | English |
| last_indexed | 2024-04-12T12:26:19Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj.art-76b1d8dc651e4e43a9fbf45be9ee8eba2022-12-22T03:33:09ZengTaylor & Francis GroupRedox Report1351-00021743-29282022-12-0127123924810.1080/13510002.2022.2109360β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury modelsQi Ding0Guodong Zhang1Yang Wang2Lei Xu3Meifei Wu4Yiwen Zhou5Tao Xu6Xiaoming Meng7Cheng Huang8Lei Zhang9Anhui No.2 Provincial People’s Hospital, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaSchool of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaBackground The restoration of the Wnt/β-catenin pathway to alleviate alcoholic fatty liver disease (AFLD) progression is under study as a new strategy for alcoholic liver disease (ALD) treatment. Recent studies have indicated that interferon-stimulated gene 15 (ISG15) can covalently bind to β-catenin by HECT E3 ubiquitin ligase 5 (HERC5), leading to ISG degradation and downregulation of β-catenin levels. However, the relationship between β-catenin and the ISG15 system in AFLD remains unclear.Methods Here, we explored the roles of the ISG15 system in β-catenin activation and in the pathogenesis of alcohol-induced liver injury and steatosis.Results In this study, HERC5 silencing upregulated β-catenin protein expression and inhibited lipid metabolism disorders and cell apoptosis. Reduced β-catenin protein expression, increased lipid metabolism disorders, and cell apoptosis were detected in cells induced with HERC5 overexpression, which was reversible with the reactive oxygen species (ROS) inhibitor. All the above results were statistically analyzed. Thus, these observations demonstrate that β-catenin ISGylation is a prominent regulator of ALD pathology, which works by regulating ROS to induce lipid metabolism disorders and cell apoptosis.Conclusion Our findings provided the mechanism involved in the β-catenin ISGylation, allowing for future studies on the prevention or amelioration of liver injury in ALD.https://www.tandfonline.com/doi/10.1080/13510002.2022.2109360Alcoholic fatty liver diseaseISG15HERC5β-catenin ISGylationROSWnt signaling pathway |
| spellingShingle | Qi Ding Guodong Zhang Yang Wang Lei Xu Meifei Wu Yiwen Zhou Tao Xu Xiaoming Meng Cheng Huang Lei Zhang β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models Redox Report Alcoholic fatty liver disease ISG15 HERC5 β-catenin ISGylation ROS Wnt signaling pathway |
| title | β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models |
| title_full | β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models |
| title_fullStr | β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models |
| title_full_unstemmed | β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models |
| title_short | β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models |
| title_sort | β catenin isgylation promotes lipid deposition and apoptosis in ethanol stimulated liver injury models |
| topic | Alcoholic fatty liver disease ISG15 HERC5 β-catenin ISGylation ROS Wnt signaling pathway |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2022.2109360 |
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