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UPA Perpustakaan Universitas Jember

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

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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.

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