miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via ATG7.

UNLABELLED

Activation of hepatic stellate cell (HSC), which is the main source of extracellular matrix, plays a pivotal role in liver fibrogenesis. Autophagy of hepatic stellate cell has been recently implicated in liver fibrosis, but the regulation of hepatic stellate cell autophagy during this process remains poorly understood. Here, we first identified miR-96-5p as an aberrantly expressed miRNA in fibrotic liver tissues. Next, we transfected miR-96-5p mimic into human hepatic stellate cell line LX-2 and observed decreased protein and mRNA levels of α-SMA and Col1A1. In addition, transfection of miR-96-5p mimic significantly reduced autophagy activity of LX-2 cells, while transfection of miR-96-5p inhibitor promoted LX-2 cell autophagy. Moreover, autophagy-related protein 7 (ATG7) was predicted as a potential target of miR-96-5p and luciferase assay confirmed its direct interaction with miR-96-5p. Finally, reintroduction of ATG7 into LX-2 cells reversed miR-96-5p-mediated inhibition of autophagy as well as α-SMA and Col1A1 expression. In conclusion, we demonstrated that miR-96-5p can inhibit hepatic stellate cell activation by blocking autophagy via ATG7. These findings provide new insight into the development of miRNA-based anti-fibrotic strategies.

KEY MESSAGES

• Altered miRNA expression profile is observed in fibrotic liver tissues. • miR-96-5p can inhibit HSC activation. • Autophagy of HSC is repressed by miR-96-5p during activation. • ATG7 is a direct target of miR-96-5p. • ATG7 can rescue miR-96-5p-mediated inhibition of autophagy and HSC activation.