title: MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: A rat fibrosis model study.
abstract: Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3'-untranslated region (3'-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3'-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-β1 (TGF-β1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Le
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Lu
authors.affiliation: West Hospital Ward 1, Shaanxi Provincial People's Hospital, No.256, Youyi Road(west), Xi'an, Shaanxi 710068, China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jiazhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004, China. Electronic address: yiminngli@163.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C569198:MIRN130 microRNA, rat; D035683:MicroRNAs; D047495:PPAR gamma
keywords: Hepatic stellate cells; Liver fibrosis; PPARγ; TGF-β1; miR-130a; miR-130b