Rho GTPases调控卡他莫拉菌侵入人呼吸道上皮细胞的机制研究

目前，10%-15%慢性阻塞性肺疾病急性加重(AECOPD)由卡他莫拉菌引起，其中卡他莫拉菌侵入人呼吸道上皮细胞是引起感染的关键环节。已有研究证明，肌动蛋白聚合状态会影响卡他莫拉菌的入侵。本课题组近期研究表明，Rho GTPases作为调控肌动蛋白聚合的重要因子，也参与调控了卡他莫拉菌的入侵，但具体机制仍不清楚。为阐明其机制，本研究采用针对Rac1和Cdc42特异性抑制剂和激动剂预处理A549细胞，然后感染卡他莫拉菌高毒株73-OR，检测卡他莫拉菌的侵入量和过程，以及对肌动蛋白单体聚合的影响；再利用siRNA分别对与肌动蛋白单体结合的效应因子进行沉默表达，然后用Rac1和Cdc42激动剂处理沉默表达细胞，并检测卡他莫拉菌的入侵，进而阐明Rho GTPases通过调控肌动蛋白聚合间接调节卡他莫拉菌入侵的机制。该研究将对通过固有免疫方式预防和治疗卡他莫拉菌引起的AECOPD提供重要理论依据。

Currently, 10%-15% of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by Moraxella catarrhalis. It has been proved that actin polymerization can affect the invasion of Moraxella catarrhalis. Recent studies of our group show that Rho GTPases, as an important factor in regulating actin polymerization, also participate in the regulation of invasion of Moraxella catarrhalis, but the specific mechanism is still unclear. In order to elucidate the mechanism, A549 cells will be pretreated with Rac1 and Cdc42 specific inhibitors and agonist, and then infected with Moraxella catarrhalis 73-OR to detect the invasion of Moraxella catarrhalis, as well as the effect on actin monomer polymerization; siRNA will be used to silence the expression of actin monomer binding effectors, and then Rac1 and Cdc42 agonist will be used and the invasion of Moraxella catarrhalis will also be detected to elucidate the mechanism of Rho GTPases indirectly regulating the invasion of Moraxella catarrhalis by regulating actin polymerization. This study will provide an important theoretical basis for the prevention or treatment of AECOPD caused by Moraxella catarrhalis.