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

被引:84
作者
Li, Fuyuan [1 ]
Ma, Ning [1 ,2 ]
Zhao, Ruiqi [1 ]
Wu, Guodong [1 ]
Zhang, Yanfen [3 ]
Qiao, Yu [1 ]
Han, Dong [1 ]
Xu, Ya [1 ]
Xiang, Ying [1 ,4 ]
Yan, Bingzhu [5 ]
Jin, Jianfeng [1 ]
Lv, Guixiang [1 ]
Wang, Lei [1 ]
Xu, Changqing [6 ]
Gao, Xu [1 ,2 ,7 ,8 ]
Luo, Shanshun [9 ]
机构
[1] Harbin Med Univ, Dept Biochem & Mol Biol, Harbin, Peoples R China
[2] Translat Med Ctr Northern China, Harbin, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp, Dept Lab Diag, Harbin, Peoples R China
[4] Yangtze Univ, Sch Med, Dept Cell Biol, Jinzhou, Peoples R China
[5] Harbin Med Univ, Affiliated Hosp 2, Dept Infect Dis, Harbin, Peoples R China
[6] Harbin Med Univ, Dept Pathophysiol, Harbin, Peoples R China
[7] Heilongjiang Med Sci Acad, Basic Med Inst, Harbin, Peoples R China
[8] Harbin Med Univ, Minist Educ, Key Lab Cardiovasc Med Res, Harbin, Peoples R China
[9] Harbin Med Univ, Affiliated Hosp 1, Dept Gerontol, Harbin, Peoples R China
关键词
liver fibrosis; microRNA; HSCs; transgenic mice; HEPATOCELLULAR-CARCINOMA; ENDOTHELIAL-CELLS; GROWTH-FACTORS; IN-VITRO; MICRORNAS; IDENTIFICATION; EXPRESSION; REVEALS; MIR-122; MODEL;
D O I
10.1111/jcmm.12293
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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- 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.
引用
收藏
页码:966 / 974
页数:9
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