State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
PLoS Negl Trop Dis. 2023 Jul 25;17(7):e0011520. doi: 10.1371/journal.pntd.0011520. eCollection 2023 Jul.
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.
肝纤维化是泡球蚴感染的组织病理学特征之一。肝星状细胞(HSCs)的激活是肝纤维化发展的关键事件。然而,泡球蚴感染诱导的肝纤维化中 HSC 激活的分子机制在很大程度上仍不清楚。在这里,我们报道了 mmu-miR-342-3p 在 HSCs 中表达最丰富,并在 HSCs 中对泡球蚴感染有反应而上调。我们进一步表明,mmu-miR-342-3p 能够与 Zbtb7a 基因的 3'UTR 结合并调节其表达。此外,在泡球蚴感染期间,mmu-miR-342-3p 的表达与 HSCs 中其靶基因 Zbtb7a 呈负相关。mmu-miR-342-3p 的敲低促进了体外激活的 HSCs 中 Gfap 的表达。在泡球蚴感染的小鼠中,mmu-miR-342-3p 的敲低抑制了α-Sma、Col1α1 和 TGF-β 的表达,但促进了 Gfap 的表达。因此,mmu-miR-342-3p 是 HSCs 激活的关键调节剂,抑制 mmu-miR-342-3p 以抑制激活的 HSCs 中 Zbtb7a 介导的 TGF-β 信号转导可能是治疗泡球蚴感染引起的肝纤维化的一种新策略。