Background The abnormal expression of microRNAs (miRNAs) was involved in the pathological process of liver fibrosis, but their accurate molecular mechanisms remain to be fully clarified.
Aim To evaluate the role of miRNA-96-5p (miR-96-5p) in hepatic stellate cells (HSCs) activation and liver fibrosis.
Methods The differentially expressed mRNAs (DEMs) and signal pathways about hepatic fibrosis were analyzed and screened from Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to evaluate the biological significance and enriched pathways of the DEMs. The upstream miRNAs of DEMs were predicted by bioinformatics websites. The regulatory effects of miRNA on liver fibrosis through the target gene were verified in HSCs and in mouse CCl\(_4\)-induced liver fibrosis models.
Results ECM-receptor interaction pathway was the most enriched pathway related to liver fibrosis through the GO and KEGG analysis of GEO database. Fibronectin1 (FN1) was up-regulated most significantly in the ECM-receptor pathway. Besides, miR-96-5p was considered to be the direct regulated miRNA of FN1 by bioinformatics websites prediction, qRT-PCR, Western blotting, and dual luciferase reporter assay. Finally, the effects of miR-96-5p up-regulation inhibit the activation of HSCs and alleviate CCl4-induced liver fibrosis by regulating FN1 and the ECM-receptor interaction pathway were confirmed in mice.
Conclusions Our findings indicate that the up-regulation of miR-96-5p can inhibit activity of HSCs and alleviate liver fibrosis by inhibiting FN1 and ECM-receptor interaction pathway.