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

文献类型： 外文期刊

作者： Cao, Shanling;Wang, Dexian;Wu, Yixuan;Zhang, Junmei;Pu, Lixia;Luo, Xuenong;Zhang, Xueyong;Sun, Xiaolin;Zheng, Yadong;Wang, Shuai;Guo, Xiaola

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期刊名称： PLOS NEGLECTED TROPICAL DISEASES

ISSN： 1935-2735

年卷期： 2023 年 17 卷 7 期

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收录情况： SCIE（2023版）

摘要： 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 & alpha;-Sma, Col1 & alpha;1, and TGF-& beta; 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 promote Zbtb7a-mediated TGF-& beta; signaling in activated HSCs could be a novel strategy to treat liver fibrosis induced by E. multilocularis. Author summaryLiver fibrosis is one of the histopathological features 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 liver fibrosis induced by E. multilocularis infection remains largely unknown. In recent years, there is increasing evidence indicate that the abnormal expression of miRNAs is closely related to the occurrence and development of liver fibrosis. The expression profile of miRNA in hepatic fibrosis induced by E. multilocularis infection has been widely characterized, but the roles of miRNAs in liver fibrosis are largely unexplored. Herein, we identified a set of differentially expressed miRNAs in the activated HSCs induced by E. multilocularis, mmu-miR-342-3p of which was dominantly expressed in HSCs. This study signifies the important role of mmu-miR-342-3p in the HSC activation, which will help us to better understand the mechanism of liver fibrosis induced by E. multilocularis infection.

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