LncRNA在PM2.5诱发呼吸系统炎性反应中的作用机制

项目名称： LncRNA在PM2.5诱发呼吸系统炎性反应中的作用机制

项目编号： No.21477045

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 彭晓武

作者单位： 生态环境部华南环境科学研究所

项目金额： 80万元

中文摘要： PM2.5是灰霾的主要成因，对呼吸系统的致炎效应是其最重要的毒理效应。炎症的发生受到表观遗传的调控，新近发现长链非编码RNA（lncRNA）可能通过对靶基因的调控在炎症发生过程中发挥关键性的作用。课题组前期研究发现lncRNA表达异常可能是PM2.5诱发炎症反应的早期分子事件。因此，本项目拟用三个区域采集的PM2.5诱导细胞和动物产生炎症反应；利用lncRNA芯片筛选关键lncRNA；运用RNA干扰和细胞转染过表达建立功能研究体系，分析lncRNA在炎症效应中的功能；通过基因芯片筛选、Western blot等方法确认lncRNA调控的靶基因和蛋白，揭示lncRNA在灰霾PM2.5致呼吸系统炎性效应中的调控机制。本研究可为炎症的治疗提供lncRNA水平上的靶点，将lncRNA这一生命科学最前沿的内容引入到环境暴露导致炎症的分子毒理学机制研究领域，为其拓展了一个新的研究方向。

中文关键词： 细颗粒物；长链非编码RNA；炎性反应；靶基因和蛋白

英文摘要： PM2.5 is a main cause of the ash haze weather, and the inflammatory effect on respiratory system is the most important toxicity caused by PM2.5.Recently, epigenetic regulation is found to be involved in the mechanism of inflammation, and it suggests that long non-coding RNA(lncRNA) may play a key role in inflammatory reaction by regulating target genes. In previous studies, we found that the abnormal expression of lncRNA may be an early molecular event of inflammation caused by PM2.5.Therefore, we will use different sources of PM2.5 to induce cell and animal to produce inflammatory reactions, and lncRNA chip will be used for screening key lncRNAs. and then, RNA interference and cell transfection will be used to establish loss-of-function and gain-of-function systems in cell lines in order to find regulatory function of lncRNAs in the inflammatory response. Furthermore, we will use gene chip and western blot to screen target genes and proteins which are regulated by lncRNAs, and finally to reveal the molecular mechanisms of inflammatory effects on respiratory system caused by PM2.5. The present study will provide targets for the treatment of inflammation at a level of lincRNA. More meaningfully, the study will introduce lncRNA, the cutting edge of new content of bioscience, into the field of molecular toxicological mechanism of inflammatory effects and provide a new research direction for this field.

英文关键词： PM2.5;LcnRNA;inflammatory effects;target gene and protein