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

作者：Shanling Cao, Dexian Wang, Yixuan Wu, Junmei Zhang, Lixia Pu, Xuenong Luo, Xueyong Zhang, Xiaolin Sun, Yadong Zheng, Shuai Wang, Xiaola Guo · 发表于：PLoS neglected tropical diseases · 年份：2023 · DOI：10.1371/journal.pntd.0011520 · 被引用次数：5 · 研究领域：Parasitic infections in humans and animals、Congenital Anomalies and Fetal Surgery、Amoebic Infections and Treatments

Liver fibrosis is one of the histopathological characters during Echinococcus multilocularis infection. 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 the E. multilocularis infection-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 to E. multilocularis infection. We further showed that mmu-miR-342-3p was able to bind to the 3' UTR of the Zbtb7a gene and regulated its expression. Moreover, mmu-miR-342-3p expression was negatively correlated with its target gene Zbtb7a in HSCs during E. multilocularis infection. Knockdown of mmu-miR-342-3p promoted the expression of Gfap in the activated HSCs in vitro. In the E. multilocularis-infected mice, knockdown of mmu-miR-342-3p suppressed the expression of α-Sma, Col1α1, and TGF-β but promoted the expression of Gfap. 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 by E. multilocularis.