具核梭杆菌通过膜蛋白FadA与CDH11结合入侵肺泡上皮细胞加重COPD的机制研究

慢性牙周炎与慢性阻塞性肺疾病（COPD）发生发展密切相关，本课题组前期研究发现牙周致病菌-具核梭杆菌（Fusobacterium nucleatum）是COPD患者肺通气功能障碍的重要危险因素，但是机制尚不明确。我们依据一系列前期探索性工作，推测F. nucleatum可能通过膜蛋白FadA与CDH11结合入侵肺泡上皮细胞，从而募集并激活MAPK13/JUN炎症信号通路，加重肺泡上皮细胞炎症反应，诱导COPD患者肺通气功能的减退。本研究拟先明确FadA是F. nucleatum入侵肺泡上皮细胞、诱导炎症反应的重要毒力因子，证实CDH11是FadA入侵肺泡上皮细胞的特异性靶点，阐明FadA与CDH11相互作用的关键氨基酸结构域及其对MAPK13/JUN炎症通路的调控机制，最后通过动物实验验证该项目假说。本项目成果将为防治F. nucleatum感染引起COPD病情加重提供新策略和新靶点。

Chronic periodontitis is closely related to the occurrence and development of chronic obstructive pulmonary disease (COPD). Our previous study demonstrates that Fusobacterium nucleatum is an important risk factor for pulmonary ventilation dysfunction in COPD patients, but the underlying mechanism is still unclear. According to a series of preliminary exploratory studies, we speculate that F. nucleatum may invade pulmonary epithelial cells through the interaction between FadA and CDH11, and then recruits and activates MAPK13/JUN inflammatory signaling pathway to aggravate inflammation of pulmonary epithelial cells and weaken pulmonary ventilation function of COPD patients. This study intends to first clarify that FadA is an important virulence factor of F. nucleatum invading pulmonary epithelial cells and inducing inflammation, confirms that CDH11 specifically interacts with FadA to facilitate F. nucleatum internalization into pulmonary epithelial cells, explores the key amino acid domain of the interaction between FadA and CDH11 and its regulation mechanism on MAPK13/JUN inflammatory signaling pathway, and finally verifies this project hypothesis through animal experiments. The results of this project will provide new strategies and new targets for the prevention and treatment of COPD exacerbation caused by F. nucleatum infection.