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

Fuyuan Li; Ning Ma; Ruiqi Zhao; Guodong Wu; Yanfen Zhang; Yu Qiao; Dong Han; Ya Xu; Ying Xiang; Bingzhu Yan; Jianfeng Jin; Guixiang Lv; Lei Wang; Changqing Xu; Xu Gao; Shanshun Luo

doi:10.1111/jcmm.12293

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

J Cell Mol Med. 2014 Jun;18(6):966-74. doi: 10.1111/jcmm.12293. Epub 2014 May 6.

Authors

Fuyuan Li¹, Ning Ma, Ruiqi Zhao, Guodong Wu, Yanfen Zhang, Yu Qiao, Dong Han, Ya Xu, Ying Xiang, Bingzhu Yan, Jianfeng Jin, Guixiang Lv, Lei Wang, Changqing Xu, Xu Gao, Shanshun Luo

Affiliation

¹ Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

Abstract

The transition from liver fibrosis to hepatocellular carcinoma (HCC) has been suggested to be a continuous and developmental pathological process. MicroRNAs (miRNAs) 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 CCl4 . 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 HSCs.

Keywords: HSCs; liver fibrosis; microRNA; transgenic mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbon Tetrachloride / toxicity
Carcinoma, Hepatocellular / etiology
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / prevention & control*
Cells, Cultured
Coculture Techniques
Hepatic Stellate Cells / cytology*
Hepatic Stellate Cells / drug effects
Hepatic Stellate Cells / metabolism
Humans
Liver Cirrhosis / chemically induced
Liver Cirrhosis / genetics
Liver Cirrhosis / prevention & control*
Liver Neoplasms / etiology
Liver Neoplasms / metabolism
Liver Neoplasms / prevention & control
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
MicroRNAs / genetics*
MicroRNAs / metabolism
Platelet-Derived Growth Factor / antagonists & inhibitors*
Platelet-Derived Growth Factor / genetics
Platelet-Derived Growth Factor / metabolism
RNA, Messenger / genetics
Rats
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors*
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Transforming Growth Factor beta / pharmacology*

Substances

MicroRNAs
Mirn483 microRNA, mouse
Platelet-Derived Growth Factor
RNA, Messenger
Transforming Growth Factor beta
Tissue Inhibitor of Metalloproteinase-2
Carbon Tetrachloride
Matrix Metalloproteinase 2