Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.
Bottom Line: MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease.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.
Affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.Show MeSH
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Mentions: The activation of HSCs is a key process during liver fibrosis in vivo. Because we observed the inhibition of α-SMA in miR-483 transgenic mice, we investigated the role of miR-483 in the activation of HSCs. First, stimulation of the human HSC cell line LX-2 with recombinant TGF-β, a major cytokine involved in HSC activation (Fig.3A and B), led to an increase in TIMP2 and PDGF-β (Fig. S2A) and significant decrease in miR-483 expression (Fig.3C). These results are consistent with the results observed for CCl4-induced liver fibrosis in transgenic mice. We then transfected either miR-483 or a control sequence into the TGF-β stimulated LX-2 cells. α-SMA was down-regulated by overexpression of miR-483 at the translational level (Fig.3D). These results are consistent with the role of miR-483 in vivo. Our data suggest that overexpression of miR-483 regulates liver fibrosis by inhibiting the activation of HSCs in transgenic mice. Next, we identified the targets of miR-483 in this regulatory process.
Affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.