MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: A rat fibrosis model study

Journal Article · Fri Sep 25 04:00:00 EDT 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.08.012· OSTI ID:22458557

Lu, Le; Wang, Jinlong; Lu, Hongwei ^[1]; Zhang, Guoyu ^[2]; Liu, Yang; Wang, Jiazhong; Zhang, Yafei; Shang, Hao; Ji, Hong; Chen, Xi; Duan, Yanxia ^[1]; Li, Yiming ^[1]

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1. Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, West 5th Road, Xi'an, Shaanxi 710004 (China)
2. West Hospital Ward 1, Shaanxi Provincial People's Hospital, No.256, Youyi Road(west), Xi'an, Shaanxi 710068 (China)

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 (CCl{sub 4}) 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. - Highlights: • MiR-130a and miR-130b are increased and PPARγ is decreased in liver fibrosis models. • MiR-130a and miR-130b decreased PPARγ by targeting the 3′-UTR of PPARγ mRNA. • MiR-130a and miR-130b enhanced HSC cell proliferation by involving Runx3. • TGF-β1 may mediate miR-130a and miR-130b overexpression.

• OSTI ID: 22458557
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 465; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BILIARY TRACT
CARBON TETRACHLORIDE
CELL CULTURES
CELL PROLIFERATION
FIBROSIS
GENES
GROWTH FACTORS
INJECTION
LIVER
MESSENGER-RNA
RATS
RECEPTORS