Pinostilbene hydrate suppresses hepatic stellate cell activation via inhibition of miR-17–5p-mediated Wnt/β-catenin pathway

Abstract

BackgroundIn the development of liver fibrosis, activated hepatic stellate cells (HSCs) contribute to the synthesis and deposition of extracellular matrix (ECM) proteins. HSC activation is considered as a central driver of liver fibrosis. Recently, microRNAs (miRNAs) have been reported to act as key regulators in HSC activation. PurposePinostilbene hydrate (PSH), a methylated derivative of resveratrol, has demonstrated anti-inflammatory, antioxidant and anti-tumour activities. However, the effects of PSH on HSC activation remain unclear. MethodsThe effects of PSH on HSC activation were examined. Moreover, the roles of WNT inhibitory factor 1 (WIF1) and miR-17–5p in the effects of PSH on HSC activation were examined. ResultsPSH induced a significant reduction in HSC proliferation. PSH also effectively inhibited HSC activation, with reduced α-SMA and collagen expression. Notably, it was found that Wnt/β-catenin signalling was involved in the effects of PSH on HSC activation. PSH resulted in Wnt/β-catenin signalling inactivation, with a reduction in TCF activity as well as β-catenin nuclear translocation. Further studies showed that PSH inhibited Wnt/β-catenin signalling via regulation of WIF1 and miR-17–5p. Reduced HSC activation caused by PSH could be restored by loss of WIF1 or miR-17–5p mimics. Luciferase reporter assays further confirmed that WIF1 was a target of miR-17–5p. ConclusionPSH has a significant protective effect against HSC activation. In addition, we demonstrate that PSH enhances WIF1 expression and inhibits Wnt/β-catenin signalling via miR-17–5p, contributing to the suppression of HSC activation.