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.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.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: To evaluate the role of miR-483 in vivo, we engineered pre-miR-483 transgenic mice, the expression of which is driven by the CAG promoter (Fig.1B). The transgenic mouse liver overexpressed miR-483-5p and miR-483-3p (Fig.1C and D). In the transgenic mice, the administration of CCl4 for 8 weeks caused less collagen deposition and an even greater reduction in α-SMA, a marker of HSC activity, compared to the CCl4-induced WT mice at both the transcriptional and translational level (Fig.2A). These changes were more prominent in the group treated with high dose CCl4 (Fig.2A). Collectively, these data demonstrate that overexpression of pre-miR-483 may inhibit liver fibrosis and that miR-483 is a protective factor against liver fibrosis.
Affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.