Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.
Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.
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DOI：
10.1111/jcmm.12293
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发表时间：
2014-06
影响因子：
5.3
通讯作者：
Luo S
中科院分区：
文献类型：
--
作者：
Li F;Ma N;Zhao R;Wu G;Zhang Y;Qiao Y;Han D;Xu Y;Xiang Y;Yan B;Jin J;Lv G;Wang L;Xu C;Gao X;Luo S
肝纤维化向肝细胞癌（HCC）转化是一个持续发展的病理过程。microRNAs（miRNAs）是最近发现的调节肝脏疾病相关基因表达的分子。许多研究表明，来源于miR-483的miR-483- 5 p和miR-483- 3 p在HCC中表达上调，其致癌靶点已被确定。然而，最近的研究表明，miR-483- 5 p/3 p在HCC样品中部分下调，并且在大鼠肝纤维化中下调。因此，miR-483在肝纤维化中的异常表达和功能仍然是难以捉摸的。在这项研究中，我们证明了miR-483在体内过表达抑制CCl 4诱导的小鼠肝纤维化。我们证明了miR-483- 5 p/3 p共同作用于两种促纤维化因子，血小板衍生生长因子-β和金属蛋白酶组织抑制剂2，其抑制肝星状细胞（HSC）LX-2的活化。我们的工作确定了通过抑制HSC的活化来调节肝纤维化的途径。
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.