Mmu-miRNA-342-3p promotes hepatic stellate cell activation and hepatic fibrosis induced by Echinococcus multilocularis infection via targeting Zbtb7a

Abstract

Liver fibrosis is one of the histopathological characters duringEchinococcus multilocularisinfection. The activation of hepatic stellate cells (HSCs) is a key event in the development of liver fibrosis. However, the molecular mechanism of HSC activation in theE.multilocularisinfection-induced liver fibrosis remains largely unclear. Here, we reported that mmu-miR-342-3p was most dominantly expressed in HSCs and was upregulated in the HSCs in response toE.multilocularisinfection. We further showed that mmu-miR-342-3p was able to bind to the 3’ UTR of theZbtb7agene and regulated its expression. Moreover, mmu-miR-342-3p expression was negatively correlated with its target geneZbtb7ain HSCs duringE.multilocularisinfection. Knockdown of mmu-miR-342-3p promoted the expression ofGfapin the activated HSCsin vitro. In theE.multilocularis-infected mice, knockdown of mmu-miR-342-3p suppressed the expression ofα-Sma,Col1α1, andTGF-βbut promoted the expression ofGfap. Therefore, mmu-miR-342-3p is a key regulator for activation of HSCs, and inhibiting mmu-miR-342-3p to suppressed Zbtb7a-mediated TGF-β signaling in activated HSCs could be a novel strategy to treat liver fibrosis induced byE.multilocularis.