miR-27b/KSRP参与调控上皮细胞对病原微生物的天然免疫反应研究

新近报道上皮细胞除了作为物理屏障外，还具备其他天然免疫策略，但存在许多重要研究空白，尤其是功能miRNAs被调控和调控下游分子的机制，目前还未有miR-27b/KSRP与H. pylori感染相互关系的报道。在申请人以第1作者发表在JI上的前期工作基础上（miR-181s调控PCAF负反馈抑制上皮细胞免疫反应），提出本项目的总体目标：探讨受NF-κB调控表达的miR-27b能否作用于KSRP影响其结合mRNA的稳定性？miR-27b能否通过KSRP参与NF-κB信号通路下游应答？miR-27b是否影响产免疫因子水平，参与上皮细胞对病原微生物的天然免疫反应？TLRs/NF-kB和miR-27b/KSRP与病原微生物刺激的天然免疫反应间是否在其他上皮细胞天然免疫应答中具有普遍性意义？该项目实施对探讨miRNAs功能、病原微生物感染机制和防治感染的相关策略提供新的思路。

Innate immunity is an evolutionarily conserved host defense mechanism against pathogenic microbes. The newest reports showed gastric epithelial cells had developed sophisticated strategies of defense to prevent pathogen invasion of host tissue beyond simply providing a physical blockade. How epithelial cells regulate innate immune responses against pathogenic microorganism infection remained an important but understudied area of research. With a long-term goal to better understand the molecular mechanisms of epithelial innate immune responses to pathogens and the relative fundamental research published in magazine JI, the overall objective of this proposal is to investigate that whether miR-27b regulated by NF-κB signal pathway effected on KSRP to make KSRP-conjugated mRNA change in epithelial cells or not. Does miR-27b involve with the innate immunity in gastric epithelial cells against pathogenic microorganism infection according to alter the expression of inflammatory factors, such as IL-8, NO, PGE2 and so on? Are there universal phenomenon that TLRs/NF-kB and miR-27b/KSRP involve with innate immunity after pathogens' stimulation in epithelial cells? The above researches are important to provide new ideas and strategies for understanding or treating pathogens infection.