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...

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Main Authors: Qi Ding (Author), Guodong Zhang (Author), Yang Wang (Author), Lei Xu (Author), Meifei Wu (Author), Yiwen Zhou (Author), Tao Xu (Author), Xiaoming Meng (Author), Cheng Huang (Author), Lei Zhang (Author)
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Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
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LEADER 00000 am a22000003u 4500
001 doaj_76b1d8dc651e4e43a9fbf45be9ee8eba
042 |a dc 
100 1 0 |a Qi Ding  |e author 
700 1 0 |a Guodong Zhang  |e author 
700 1 0 |a Yang Wang  |e author 
700 1 0 |a Lei Xu  |e author 
700 1 0 |a Meifei Wu  |e author 
700 1 0 |a Yiwen Zhou  |e author 
700 1 0 |a Tao Xu  |e author 
700 1 0 |a Xiaoming Meng  |e author 
700 1 0 |a Cheng Huang  |e author 
700 1 0 |a Lei Zhang  |e author 
245 0 0 |a β-catenin ISGylation promotes lipid deposition and apoptosis in ethanol-stimulated liver injury models 
260 |b Taylor & Francis Group,   |c 2022-12-01T00:00:00Z. 
500 |a 10.1080/13510002.2022.2109360 
500 |a 1743-2928 
500 |a 1351-0002 
520 |a 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. 
546 |a EN 
690 |a Alcoholic fatty liver disease 
690 |a ISG15 
690 |a HERC5 
690 |a β-catenin ISGylation 
690 |a ROS 
690 |a Wnt signaling pathway 
690 |a Pathology 
690 |a RB1-214 
690 |a Biology (General) 
690 |a QH301-705.5 
655 7 |a article  |2 local 
786 0 |n Redox Report, Vol 27, Iss 1, Pp 239-248 (2022) 
787 0 |n https://www.tandfonline.com/doi/10.1080/13510002.2022.2109360 
787 0 |n https://doaj.org/toc/1351-0002 
787 0 |n https://doaj.org/toc/1743-2928 
856 4 1 |u https://doaj.org/article/76b1d8dc651e4e43a9fbf45be9ee8eba  |z Connect to this object online.