Effect of resveratrol on liver fibrosis through regulating hepatic stellate cell activation by macrophage-derived extracellular vesicles

Objective: To investigate the mechanism of resveratrol(RSV) on the activation of hepatic stellate cells by regulating macrophages. Methods: Exosomes were extracted from blank(NC-E) group and resveratroltreated(RSV-E) group by ultracentrifugation method, and the extracts were identified. The exosomes from the NC-E group and the RSV-E group were co-cultured with growth factor-β1(TGF-β1)-activated hepatic stellate cells JS-1 and divided into control group, TGF-β1-activated group(TGF-β1 group), NC-E+TGF-β1-activated group(NC-E+TGF-β1 group) and RSV-E+TGF-β1-activated group(RSV-E+TGF-β1 group). Immunofluorescence, real-time fluorescence quantitative PCR(RT-qPCR) and western blotting were used to detect the alphasmooth muscle actin(α-SMA) and type I collagen alpha 1 chain(Col1a1). Western blotting was also used to detect the expression of autophagy-related indicators Beclin1 and LC3 Ⅰ/Ⅱ. Results: Compared with the control group, the TGF-β1 group showed increased expression levels of α-SMA, Col1a1, Beclin1 and LC3 Ⅰ/Ⅱ(P<0.05). Compared with the TGF-β1 group, the RSV-E+TGF-β1 group showed decreased expression levels of α-SMA, Col1a1, Beclin1 and LC3 Ⅰ/Ⅱ(P<0.05), while the NC-E+TGF-β1 group and TGF-β1 group showed no significant difference(P>0.05). Conclusion: RSV may inhibit the progression of liver fibrosis by regulating macrophage-derived extracellular vesicles and its mechanism may be related to the inhibition of autophagy in hepatic stellate cells.