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Abstract

The Role and Molecular Regulatory Mechanism of A Disintegrin and Metalloprotease 9 in Alcoholic Liver Fibrosis

Author(s): Xiao Gai Song, S. Q. Li*, Meng Li Yang, L. N. Wang, Lu Liu, L. C. Yuan, X. Y. Zhang, B. B. Zhang and Qian Hui Li
Department of Hepatology, The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, 1The Second Affiliated Hospital of Henan University of Science and Technology, 2Henan Center for Engineering and Technology Research on Prevention and treatment of Liver Diseases, Luoyang 471003, 3Luoyang Polytechnic, Luoyang 471934, 4The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471023, China

Correspondence Address:
S. Q. LI, Henan Center for Engineering and Technology Research on Prevention and treatment of Liver Diseases, Luoyang 471003, China, E-mail: [email protected]


A disintegrin and metalloprotease 9 has been reported to play a key role in many diseases. However, the underlying effects and mechanisms of a disintegrin and metalloprotease 9 in alcoholic liver fibrosis have not been well understood. To investigate the role of a disintegrin and metalloprotease 9 and its regulatory molecular mechanism in alcoholic liver fibrosis, a single guide ribonucleic acid targeting the a disintegrin and metalloprotease 9 sequence of mice was adopted by clustered regularly interspaced short palindromic repeats/Cas9 technology to inhibit its expression in this study. Subsequently, hepatic stellate cell-T6 and male mice C57BL/6J were respectively divided into 4 groups and each group was treated differently. In vivo experiment, the normal group was fed with control Lieber-DeCarli TP4030C; the saline+alcohol group was injected with saline; the A disintegrin and metalloprotease 9-single guide ribonucleic acid+alcohol group was injected with effective single guide ribonucleic acid plasmids and the c-Jun N-terminal kinase inhibitor+alcohol group was injected with c-Jun N-terminal kinase inhibitor SP600125. All mice except for the normal group received Lieber-DeCarli TP4030A and carbon tetrachloride. Furthermore, examination of serum aspartate transaminase and alanine transaminase activities and the pathological analysis by hematoxylin-eosin staining, picric acid-sirius red staining, Hoechst 33 258 staining confirmed the pro-fibro genic effect of a disintegrin and metalloprotease 9. Compared with the saline+alcohol group, the levels and the expression of a disintegrin and metalloprotease 9, p-c-Jun, cytochrome P450 2E1, tumor necrosis factor alpha, alpha-smooth-muscle actin and Bcl-2-associated X in the A disintegrin and metalloprotease 9- single guide ribonucleic acid+alcohol group and the c-Jun N-terminal kinase inhibitor+alcohol group decreased significantly (p<0.05 or p<0.01), while the expression of heat shock protein 70, proliferating cell nuclear antigen and vascular endothelial growth factor increased significantly (p<0.05 or p<0.01). In addition, the disintegrin and metalloprotease 9-single guide ribonucleic acid+alcohol group and the c-Jun N-terminal kinase inhibitor+alcohol group in vitro experiment could inhibit the proliferation of hepatic stellate cells and promote apoptosis. Collectively, our results indicated that a disintegrin and metalloprotease 9 could promote alcoholic liver fibrosis in mice by activating the c-Jun N-terminal kinase signaling pathway, which is expected to make a breakthrough in the gene therapy of alcoholic liver fibrosis.

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