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

الملخص EN

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.