LAUSR

Hepatic stellate cells (HSCs) are the major source of extracellular matrix (ECM)-producing myofibroblasts. When activated by multiple injuries, HSCs become proliferative, contractile, inflammatory and chemotactic and are characterized by enhanced ECM production, which plays a central role in hepatic fibrosis initiation and progression. In the present study, through bioinformatics analysis, we identified the abnormal upregulation of Peripheral Myelin Protein 22 (PMP22) in fibrotic murine liver. In CCl4-induced hepatic fibrosis model in mice and TGF-β-activated hHSCs, PMP22 was observed remarkably upregulated. In TGF-β-stimulated hHSCs, PMP22 silencing hindered, whereas PMP22 overexpression aggravated TGF-β-induced hHSC activation. In CCl4-induced hepatic fibrosis model in mice, PMP22 silencing improved CCl4-caused liver damage and fibrotic changes. Through online tools prediction and experimental validation, miR-139-5p was found to bind to the 3'UTR of PMP22 and negatively regulate the expression of PMP22. In contrast to PMP22 silencing, miR-139-5p inhibition enhanced TGF-β-induced hHSC activation; the effects of miR-139-5p inhibition on TGF-β-induced hHSC activation were partially reversed by PMP22 silencing. In conclusion, we identify the abnormal upregulation of PMP22 in TGF-β-activated HSCs and CCl4-induced hepatic fibrosis model in mice, as well as the pro-fibrotic role of PMP22 through aggravating TGF-β-induced HSCs activation. miR-139-5p targets the 3'UTR of PMP22 and inhibits PMP22 expression; miR-139-5p hinders TGF-β-induced HSCs activation through targeting PMP22.