Overexpression miR-125a-5p inhibits HSCs activation and alleviates liver fibrosis through TGF-β/Smad2/3 signaling pathway and autophagy.

Liver fibrosis represents an important pathological stage during chronic hepatopathy development, posing a significant threat to human health. Hepatic stellate cells (HSCs), an essential hepatic non-parenchymal cells, have a key effect on fibrogenesis, with their activation being a hallmark of liver fibrosis. MicroRNAs (miRNAs), the small non-coding RNAs, become the critical biomarkers and regulatory molecules in fibrotic processes. Among them, miR-125a-5p is implicated in cancer and inflammatory pathways, yet its functional role and mechanistic involvement in HSC activation remain poorly understood. According to our findings, miR-125a-5p expression was significantly decreased in TGF-β-activated HSC-T6 cells. Notably, ectopic miR-125a-5p overexpression effectively inhibited TGF-β-mediated HSC-T6 activation. Further mechanistic investigations revealed that miR-125a-5p attenuated HSC activation while ameliorating liver fibrosis through regulating the TGF-β/Smad2/3 pathway and autophagy. Additionally, TGFβR1 was miR-125a-5p's target gene. Collectively, miR-125a-5p negatively regulates HSC activation in liver fibrosis, exerting its anti-fibrotic activities through suppressing the TGF-β/Smad2/3 pathway and autophagy modulation.