ADAM8 promotes alcoholic liver fibrosis through the MAPK signaling pathway.

Autor: Yang M; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Li S; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China. sanqiangli2001@163.com.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China. sanqiangli2001@163.com., Luo R; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Zhao Y; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Sun Y; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Li H; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Cui Q; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Wu J; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China., Mao L; The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 KaiYuan Road, Luoyang, 471000, Henan, China. longfeimao2022@163.com.; Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases, Luoyang, 471000, Henan, China. longfeimao2022@163.com.
Jazyk: angličtina
Zdroj: The journal of physiological sciences : JPS [J Physiol Sci] 2024 Oct 16; Vol. 74 (1), pp. 52. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1186/s12576-024-00943-2
Abstrakt: The effect and molecular regulatory mechanism of A Disintegrin and Metalloproteinase 8 (ADAM8) were explored in alcoholic liver fibrosis (ALF). C57BL/6N male mice were randomly divided into control, alcohol, and ADAM8-sgRNA3 plasmid groups. The control group received control liquid diet, while the alcohol and ADAM8-sgRNA3 plasmid groups were given alcohol liquid feed diet combined with ethanol gavage treatment for 8 weeks to induce ALF modeling. In addition, the ADAM8-sgRNA3 plasmid group was injected with the effective ADAM8-sgRNA3 plasmid, while the alcohol and control group mice were injected with an equivalent amount of physiological saline. LX-2 human hepatic stellate cells were divided into control, alcohol, si-ADAM8-2, and si-ADAM8-NC groups and induced for 48 h for model establishment in vitro. Serological detection, pathological staining, Western blotting, qRT-PCR and CCK8 assay were performed for experiments. Compared with the alcohol group, ADAM8 mRNA, protein and, positive area rate, serological indicators, pathological changes, and the expression of liver fibrosis marker and MAPK signaling pathway-related factors in the ADAM8-sgRNA3 plasmid group significantly decreased in vivo. Compared with the alcohol group, ADAM8 mRNA and protein expression, cell viability, and the expression of liver fibrosis markers and MAPK signaling pathway-related factors (p-ERK1/2, PCNA, Bcl-2, p-c-Jun, TGFβ1, p-p38 MAPK and HSP27) reduced significantly in the si-ADAM8-2 group. Therefore, ADAM8 promotes ALF through the MAPK signaling pathway, a promising target for treating ALF.
(© 2024. The Author(s).)
Databáze: MEDLINE
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