日本血吸虫非编码RNA跨物种调控血吸虫病肝纤维化及其机制研究

日本血吸虫miRNA（sja-miRNA）在感染过程中能分泌至宿主体液或进入宿主细胞并以跨物种方式调控基因表达。肝星状细胞（HSC）的活化是血吸虫病肝纤维化的关键环节。据此，本项目提出假说：虫源sja-miRNA在感染过程中能进入宿主HSC并调控肝纤维化的发生发展。对此，本项目将利用深度测序技术分析存在感染小鼠HSC中的Sja-miRNA，并采用体外细胞物模型筛选具有调控肝纤维化作用的Sja-miRNA。以重组腺相关病毒（rAAV）为载体，通过体内过表达和吸附Sja-miRNA干预实验，研究其对血吸虫病肝纤维化发生发展的影响，鉴定各功能虫源miRNA的靶基因并阐明其分子机制。本研究预期结果将阐明虫源Sja-miRNA直接参与调控血吸虫病肝纤维化发生发展，从而拓展了我们对血吸虫病致病机制的认识，并为肝纤维化治疗干预提供新的靶点

Schistosoma japonicum miRNA (sja-miRNA)can be secreted into body liquid or entering host cells during the infection to regulate host gene expression in a cross-species manner. Activation of hepatic stellate cells (HSCs) is essential for hepatic fibrosis. Therefore, we proposed a hypothesis that in the schistosome infection, the parasite-derived miRNAs(Sja-miRNA) enter host HSCs and regulate the occrrance and progression of the hepatic fibrosis. Therefore, in this study we will use deep-sequencing approach to detect Sja-miRNAs that are present in the HSC and Kupffer cell of infected mice. Those Sja-miRNAs will be identified that potentially regulate the fibrosis using in vitro cell models. Effects of the Sja-miRNAs on the hepatic fibrosis in mice will be investigated through recombinant adeno-associated virus (rAAV)-mediated overexpression and inhibition of specific Sja-miRNAs in naïve or infected mouse models. Further studies will be conducted to reveal the molecular mechanism underpinning the effects of the Sja-miRNAs on hepatic fibrosis. The outcomes from this study would reveal that the pathogen-derived small non-coding RNAs be involved in the cross-species regulation of hepatic fibrosis progression, which provide new insights into the pathologic mechanism of hepatic schistosomiasis. The efficient and sustained inhibition of Sja-miRNAs may present a promising therapeutic intervention for infectious diseases.