miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4

Shuxia Tian; Min Chen; Bing Wang; Yonglong Han; Haonan Shang; Junming Chen

doi:10.1155/2020/5346573

miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4

Gastroenterol Res Pract. 2020 Jun 10:2020:5346573. doi: 10.1155/2020/5346573. eCollection 2020.

Authors

Shuxia Tian¹, Min Chen¹, Bing Wang², Yonglong Han², Haonan Shang², Junming Chen^{1

2}

Affiliations

¹ Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, China.
² Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.

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.