title: Overexpression of miR-483-5p/3p cooperate to inhibit mouse liver fibrosis by suppressing the TGF-β stimulated HSCs in transgenic mice.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Fuyuan
authors.initials: F
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Zhao
authors.forename: Guodong
authors.initials: G
authors.lastname: Wu
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.forename: Bingzhu
authors.initials: B
authors.lastname: Yan
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Jin
authors.forename: Guixiang
authors.initials: G
authors.lastname: Lv
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Shanshun
authors.initials: S
authors.lastname: Luo
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D018920:Coculture Techniques; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D035683:MicroRNAs; C548913:Mirn483 microRNA, mouse; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D002251:Carbon Tetrachloride; D020778:Matrix Metalloproteinase 2
keywords: HSCs; liver fibrosis; microRNA; transgenic mice