Liver fibrosis is a common pathological process of end-stage
liver diseases. However, the role of
microRNA (
miRNA) in
liver fibrosis is poorly understood. The activated hepatic stellate cells (HSCs) are the major source of fibrogenic cells and play a central role in
liver fibrosis. In this study, we investigated the differential expression of
miRNAs in resting and
transforming growth factor β1 (TGF-β1) activated HSCs by microarray analysis and found that miR-455-3p was significantly downregulated during HSCs activation. In addition, the reduction of miR-455-3p was correlated with
liver fibrosis in mice with
carbon tetrachloride (CCl4), bile duct
ligation (BDL), and high-fat diet (HFD)-induced
liver fibrosis. Our functional analyses demonstrated that miR-455-3p inhibited expression of profibrotic markers and cell proliferation in HSCs in vitro. Moreover, miR-455-3p regulated heat shock factor 1 (HSF1) expression by binding to the
3' UTR of its
mRNA directly. Overexpression of HSF1 facilitated HSCs activation and proliferation by promoting
heat shock protein 47 (Hsp47) expression, leading to activation of the TGF-β/Smad4 signaling pathway. To explore the clinical potential of miR-455-3p, we injected ago-miR-455-3p into mice with CCl4-, BDL-, and HFD-induced hepatic
fibrosis in vivo. The overexpression of miR-455-3p suppressed HSF1 expression and reduced
fibrosis marker expression, which resulted in alleviated
liver fibrosis in mice. In conclusion, our present study suggests that miR-455-3p inhibits the activation of HSCs through targeting HSF1 involved in the Hsp47/TGF-β/Smad4 signaling pathway. Therefore, miR-455-3p might be a promising therapeutic target for
liver fibrosis.