既往研究认为PM2.5暴露通过气道上皮细胞EMT介导气道重塑引起COPD发生，但传统基于基因转录、蛋白质翻译过程的调控仍无法完全解释PM2.5致EMT的具体机制。RNA乙酰化(ac4c)作为一种新兴RNA水平调控机制，通过调节mRNA剪切、稳定等过程在机体多种生命过程发挥重要作用。申请人前期研究发现在PM2.5诱导气道上皮细胞EMT过程中RNA乙酰转移酶NAT10表达上调，其靶基因TGFβ1 mRNA发生乙酰化修饰且表达增加。本研究拟通过建立PM2.5细胞染毒和COPD小鼠模型、NAT10过表达和敲减细胞和小鼠验证NAT10在PM2.5致COPD中的作用；RNA免疫共沉淀、报告基因等手段研究NAT10调节TGFβ1 mRNA乙酰化介导气道上皮细胞EMT，参与PM2.5致COPD的分子机制。通过上述研究，丰富PM2.5毒效应机制研究体系，为阐明PM2.5致COPD的机制提供新的研究策略。

Previous studies have shown that PM2.5 exposure might induce COPD through airway remodeling mediated by EMT of airway epithelial cells. However, the regulation pattern based on the gene transcription and protein translation cannot fully explain the specific mechanism for PM2.5-induced EMT. N4-acetylcytosine RNA acetylation (ac4c), as an emerging regulatory mechanism in RNA, plays an important role in various life processes by regulating mRNA splicing and stability. Our previous study found that the expression of NAT10, and the ac4c levels and expression of TGFβ1 mRNA were up-regulated during airway epithelial cell EMT induced by PM2.5. In this program, airway epithelial cells were acutely and chronically exposed to PM2.5 to set up in vitro model; mice were exposed to PM2.5 by intratracheal instillation, whole body on-line exposure to set up COPD mouse model. NAT10 overexpression and knockdown of cells and mice were used to validate the regulation of NAT10 on the development of PM2.5-induced COPD. RNA immunoprecipitation and reporter gene were used to explore the molecular mechanism of NAT10 on regulating TGFβ1 mRNA acetylation in PM2.5-induced EMT and COPD. Our program is supposed to enrich the research system for the toxic effects of PM2.5 and provide a new strategy for clarifying molecules mechanism in PM2.5-induced COPD.