环状RNA参与血吸虫肝脏纤维化形成和发展的作用及机制研究

肝脏纤维化长期不断发展将导致其结构破坏和功能的丧失，目前其关键的分子机制仍不完全清楚。环状RNA在纤维化中的研究虽处初级阶段，但已有的研究已经有助于理解其在纤维化形成和发展中的价值。迄今为止尚未见环状RNA参与血吸虫感染导致肝脏纤维化形成的报道。本项目在已有研究基础上拟首先通过肝星状细胞高通量测序，q-PCR以及过表或消减等技术进一步验证环状RNA参与血吸虫感染肝脏纤维化的发生发展；然后采用Ago2-RIP、RNA pull down、双荧光素酶报告基因、RIP和EMSA等实验在细胞水平证明其可能通过竞争微小RNA作用或与蛋白相互作用的机制；再在血吸虫感染动物体内消减靶标分子后检测肝纤维化形成和发展相关因素；最后确定靶标circRNA同源的人源性circRNA存在于人肝脏纤维化标本上。关键环状RNA参与血吸虫肝脏纤维化形成和发展新机制的阐明，将为干预血吸虫肝脏纤维化的发生发展提供新的靶点。

The lasting development of liver fibrosis will eventually lead to the destruction of organ structure and loss of function. Although the research of circRNA in fibrosis is in the primary stage, the previous research has been helpful to understand the value of circRNA in the formation and development of fibrosis. circRNAs are thought to be related to the activation of stellate cells in liver fibrosis and may be a potential target to inhibit the development of liver fibrosis. Up to now, circRNAs have not been reported to be involved in liver fibrosis caused by schistosoma infection. On the basis of the our existing studies, this project intends to further verify the involvement of circRNAs in the occurrence and development of liver fibrosis caused by schistosoma infection through high-throughput sequencing, q-PCR, gene over-expression or gene knock down techniques. Then, the Ago2-RIP experiment, RNA pull down, double luciferase reporter gene, RIP, EMSA and other experiments were used to prove that it may compete for the action of microRNAs or interact with proteins at the level of hepatic stellate cells. The factors related to the formation and development of liver fibrosis were detected in schistosomiasis infected animals after knock down target molecules. Finally, it was determined that the homologous human circRNA of the target circRNA existed in the human liver fibrosis specimens. Elucidating the new mechanism of the involvement of key circRNAs in the formation and development of schistosomiasis liver fibrosis will provide a new target for the intervention and treatment of schistosomiasis liver fibrosis.