Department of Tropical Diseases, Naval Medical University, Shanghai, China.
Front Cell Infect Microbiol. 2020 Mar 13;10:101. doi: 10.3389/fcimb.2020.00101. eCollection 2020.
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 (Sja-miR-1) exists in the hepatic stellate cells (HSCs) of mice infected with the parasite and up-regulates the expression of collagens and α-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/β-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.
血吸虫病仍然是一种严重的寄生虫病，其特征是肉芽肿性炎症和肝纤维化。寄生虫来源的 microRNAs 可以调节宿主基因和细胞表型。在这里，我们表明，一种源自 (Sja-miR-1) 的 microRNA 存在于感染寄生虫的小鼠的肝星状细胞 (HSCs) 中，并通过靶向分泌卷曲相关蛋白 1 (SFRP1) 上调胶原蛋白和 α-SMA 的表达。载体介导的 Sja-miR-1 递送至幼稚小鼠导致小鼠肝纤维化。因此，在感染小鼠中抑制 Sja-miR-1 可减少寄生虫诱导的肝纤维化。Sja-miR-1 介导的 HSC 激活的机制可能是通过靶向 SFRP1 来调节 Wnt/β-catenin 通路。这些发现表明寄生虫来源的小非编码 RNA 参与了宿主病理过程的跨物种调节，持久抑制 Sja-miR-1 可能为寄生虫病提供治疗潜力。
