COPD发病机制中，气道炎症难以解释疾病临床表型及合并症多样是目前研究的瓶颈。我们前期研究发现MEF2不仅在上皮细胞中表达，而且与COPD气道炎症及能量代谢相关，但是作用机制不清。本课题提出MEF2作为气道炎症与能量代谢的开关参与COPD发病的假说。我们假设，MEF2的磷酸化与去磷酸化形式决定了其在COPD气道炎症始动阶段参与能量代谢或免疫调控网络。为验证这个假说，本课题拟分离培养COPD患者及模型大鼠的原代气道上皮细胞，阐明COPD中MEF2的特异性表达及功能特征。在体外研究中构建MEF2稳转细胞株，通过染色质免疫共沉淀结合测序技术及串联亲和液相质谱分析探索MEF2作为转录因子的下游靶基因以及转录复合体组分。本课题将从分子、细胞及整体水平多方面探讨MEF2作为免疫代谢开关在COPD气道炎症中的作用和分子机制，并从免疫代谢开关这个新视点为COPD气道炎症的调控提供理论基础及新思路。

Previous studies on Chronic Obstructive Pulmonary Disease (COPD) have mainly focused on airway inflammation as the primary pathogenesis. The causative factors of multiple phenotypes COPD and comorbid diseases such as metabolic syndrome have yet to be clarified. Our previous study detected the expression of MEF2 in bronchial epithelia and its corresponding effect on airway inflammation and metabolism, leading to the hypothesis of MEF2 as a plausible immune-metabolic switch in the pathogenesis of COPD. MEF2 may exist in two states with distinct physiological activities. In healthy individuals, MEF2 is phosphorylated and can promote the expression of its metabolic targets. On the contrary, MEF2 is dephosphorylated and can promote airway inflammation in COPD patients. To identify this assumption, we attempt to isolate and culture bronchial epithelial cells from COPD patients and rat models to examine the key subtype and function in COPD through clinical and in vivo experiments. Furthermore, we propose to establish Flag-MEF2-16HBE and TAP-MEF2-16HBE stable cell strains and identify the target genes and transcription complex of MEF2 through in vitro experiments. This study will allow us to explore the potential mechanisms of MEF2 in airway inflammation and metabolism in COPD, providing new insights on COPD pathogenesis and new strategies for clinical treatment.