A MicroRNA Derived From Schistosoma japonicum Promotes Schistosomiasis Hepatic Fibrosis by Targeting Host Secreted Frizzled-Related Protein 1
A MicroRNA Derived From Schistosoma japonicum Promotes Schistosomiasis Hepatic Fibrosis by Targeting Host Secreted Frizzled-Related Protein 1
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DOI：
10.3389/fcimb.2020.00101
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发表时间：
2020-03-13
影响因子：
5.7
通讯作者：
Pan Weiqing
中科院分区：
文献类型：
--
作者：
Wang Yange;Fan Xiaobin;Pan Weiqing
血吸虫病是一种严重的寄生虫病，以肉芽肿性炎症和肝纤维化为特征。来源于寄生虫的microRNA可以调节宿主基因和细胞表型。在这里，我们发现一个来自S.日本血吸虫（Sja-miR-1）存在于感染该寄生虫的小鼠肝星状细胞（HSC）中，并通过靶向分泌型卷曲相关蛋白1（SFRP 1）上调胶原和α-SMA的表达。载体介导的将Sja-miR-1递送到幼稚小鼠中导致小鼠的肝纤维化。因此，在感染小鼠中抑制Sja-miR-1导致寄生虫诱导的肝纤维化减少。Sja-miR-1激活HSC的机制可能是通过靶向SFRP 1调节Wnt/beta-catenin通路。这些发现表明寄生虫来源的小分子非编码RNA参与了宿主病理过程的跨物种调节，持续抑制Sja-miR-1可能为寄生虫病提供治疗潜力。
Schistosomiasis remains a serious parasitic disease, which is characterized by granulomatous inflammation and hepatic fibrosis. MicroRNAs derived from parasites can regulate host genes and cell phenotype. Here, we showed that a miRNA derived from S. japonicum (Sja-miR-1) exists in the hepatic stellate cells (HSCs) of mice infected with the parasite and up-regulates the expression of collagens and alpha-SMA by targeting secreted frizzled-related protein 1 (SFRP1). A vector-mediated delivery of Sja-miR-1 into naive mice led to hepatic fibrogenesis in the mice. Accordingly, inhibition of Sja-miR-1 in the infected mice led to reduction of the parasite-induced hepatic fibrosis. The mechanism behind the Sja-miR-1-mediated activation of HSC could be through targeting SFRP1 to regulate the Wnt/beta-catenin pathway. These findings reveal that parasite-derived small non-coding RNAs are implicated in cross-species regulation of host pathological process and persistent inhibition of Sja-miR-1 may provide a therapeutic potential for the parasite diseases.