Overexpression of miR‐483‐5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF ‐β stimulated HSC s in transgenic mice

• Published in: Journal of cellular and molecular medicine 2014-06, Vol.18 (6), p.966-974
• Main Authors: Li, Fuyuan, Ma, Ning, Zhao, Ruiqi, Wu, Guodong, Zhang, Yanfen, Qiao, Yu, Han, Dong, Xu, Ya, Xiang, Ying, Yan, Bingzhu, Jin, Jianfeng, Lv, Guixiang, Wang, Lei, Xu, Changqing, Gao, Xu, Luo, Shanshun
• Format: Article
• Language: English
• Subjects: Activation; Bile; Carbon tetrachloride; Cell activation; Fibrosis; Gene expression; Gene therapy; Growth factors; Hepatitis; Hepatocellular carcinoma; Liver; Liver cancer; Liver diseases; Metalloproteinase; MicroRNAs; miRNA; Stellate cells; Tissue inhibitor of metalloproteinase 2; Transgenic animals; Transgenic mice
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12293

The transition from liver fibrosis to hepatocellular carcinoma ( HCC ) has been suggested to be a continuous and developmental pathological process. Micro RNA s (mi RNA s) are recently discovered molecules that regulate the expression of genes involved in liver disease. Many reports demonstrate that miR‐483‐5p and miR‐483‐3p, which originate from miR‐483, are up‐regulated in HCC , and their oncogenic targets have been identified. However, recent studies have suggested that miR‐483‐5p/3p is partially down‐regulated in HCC samples and is down‐regulated in rat liver fibrosis. Therefore, the aberrant expression and function of miR‐483 in liver fibrosis remains elusive. In this study, we demonstrate that overexpression of miR‐483 in vivo inhibits mouse liver fibrosis induced by CC l 4 . We demonstrate that miR‐483‐5p/3p acts together to target two pro‐fibrosis factors, platelet‐derived growth factor‐β and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells ( HSC ) LX ‐2. Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSC s.