RasGRP1特异性调控IL-6的表达及其在炎症性肠病中的作用研究

Overproduction of interleukin 6 (IL-6) is well known to be involved in the pathogenesis of inflammatory bowel disease (IBD) via mediating chronic inflammation. However, the specific regulation mechanism of IL-6 has not been fully understood. In our previous study, we found that microRNA let-7 can effectively inhibit the expression of IL-6. we picked 14 significant up-regulated genes in LPS-stimulated macrophages from the 2380 microRNA let-7 target-genes via gene chip and confirmed that RasGRP1 can also be regulated by microRNA let-7. Besides, we observed that both RasGRP1 and IL-6 are significantly up-regulated in the pathogenesis of IBD induced by DSS. We suppose that RasGRP1 may functions as a competing endogenous RNA to specially regulate the expression of IL-6 to induce the generation of IBD. This study will aim at analyzing the specific regulation mechanism of IL-6 and the function of RasGRP1 in the development of IBD. The results of this project may reveal a novel mechanism for the progression of IBD and may provide a new clue for the diagnosis and treatment of this disease.

促炎性细胞因子IL-6被认为介导了机体的慢性炎症并促进了炎症性肠病（Inflammatory bowel disease, IBD）的发生。然而目前对IL-6的特异性表达调控机制还不是很清楚。我们前期的研究结果显示RasGRP1和IL-6都受到microRNA Let-7调控，并且两者在固有免疫应答以及 IBD的发生过程中都发生了显著上调，这种表达时序性符合竞争性内源RNAs (conpeting endogenous RNAs, ceRNAs) 的作用特点：即互为ceRNAs的两个分子会同时表达上调。因此，我们推测RasGRP1分子有可能通过microRNA Let-7以一种ceRNAs方式特异性地调控IL-6的表达，并进而影响IBD的发生。本项目将从ceRNAs角度讨探RasGRP1在IBD发生过程中的作用，以期为IBD的防治提供新的作用靶点。

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