<i>Glycyrrhetinic Acid</i>‐Induced MiR‐663a Alleviates Hepatic Stellate Cell Activation by Attenuating the TGF‐<i>β</i>/Smad Signaling Pathway
Xin-Xin Guo, Wen-Na Yang, Ben-Sheng Dong, Jiawei Shang, Shi-Bing Su, Xiuli Yan, Hui Zhang
Abstract
Glycyrrhetinic acid (GA), a hydrolysate of glycyrrhizic acid from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR‐663a and its roles in TGF‐ β ‐1‐induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR‐663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR‐663a expression was downregulated in TGF‐ β ‐treated HSCs. The overexpression of miR‐663a inhibited HSC proliferation. TGF‐ β ‐1was confirmed as a direct target gene of miR‐663a. MiR‐663a alleviated HSC activation, concomitant with decreased expression of α ‐smooth muscle actin ( α ‐SMA), human α 2 (I) collagen (COL1A2), TGF‐ β 1, TGF‐ β RI, Smad4, p‐Smad2, and p‐Smad3. GA upregulated miR‐663a expression and inhibited the TGF‐ β /Smad pathway in HSCs. Further studies showed that miR‐663a inhibitor treatment reversed GA‐mediated downregulation of TGF‐ β 1, TGF‐ β RI, Smad4, p‐Smad2, p‐Smad3, α ‐SMA, and CoL1A2 in TGF‐ β 1‐treated HSCs. These results show that miR‐663a suppresses HSC proliferation and activation and the TGF‐ β /Smad signaling pathway, highlighting that miR‐663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR‐663a/TGF‐ β /Smad signaling pathway.