MiR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4. (10th June 2020)

• Record Type: Journal Article
• Authors: Tian, Shuxia; Chen, Min; Wang, Bing; Han, Yonglong; Shang, Haonan; Chen, Junming
• Other Names: Pilone Vincenzo Academic Editor.
• Is Part Of: Gastroenterology research and practice. Volume 2020(2020)
• Publication Date: 2020-06-10
• Subjects: Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; 616.33005
• DOI: 10.1155/2020/5346573
• Languages: English
• ISSNs: 1687-6121

Abstract

Abstract : Aims . Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis. Methods . TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3 ′ -untranslated region (3 ′ -UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay. Results . FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3 ′ -UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p. Conclusion . miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4.