铜绿假单胞菌(PA)极易在结构性肺病患者气道中定植与感染，导致支气管纤维化形成。气道上皮细胞-间充质细胞转化(EMT)在支气管纤维化过程中起关键作用。有关PA分泌毒力因子致支气管上皮细胞EMT的相关研究未见文献报道。我们前期研究发现：PA分泌的PA3611蛋白刺激支气管上皮细胞后，细胞形态及标记物水平的显著变化均提示EMT发生；且刺激组TGF-ß1显著提高、IκBα显著降低、NF-κB p65亚基磷酸化显著增强；此外，刺激组细胞 miRNA-144 及 miRNA-642 表达显著上升，p38 MAPK 磷酸化显著增高。据此，我们拟通过体内外研究证实如下机制：PA感染支气管上皮细胞后，PA3611 蛋白通过激活p38 MAPK信号分子，刺激miRNA-144及miRNA-642表达上调，后两者靶向抑制 IκBα，促进NF-κB p65活化与TGF-ß1合成，最终诱导支气管上皮细胞EMT。

Pseudomonas aeruginosa (PA) is one of the important pathogens, which has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases, and further lead to bronchial fibrosis. Epithelial-Mesenchymal Transition (EMT) of bronchial epithelial cells plays a vital role in the process of bronchial fibrosis. Up to the present, the research on bronchial epithelial EMT caused by secreted virulence factors of PA has not been reported. In our previous studies, we found that PA3611 protein stimulation induced the morphologic change of cultured HBECs from polygon to fusiform or spindle, as well as the up-regulation of mesenchymal cell markers and down-regulation of epithelial cell markers. Meantime, TGF-β1 secretion was markedly increased, IκBα expression was significantly decreased, and NF-κB p65 subunit phosphorylation was markedly enhanced. In addition, the levels of miR-144 and miR-642 expression and p38 MAPK phosphorylation were obviously increased in HBECs after PA3611 stimulation. Therefore, we attempt to confirm the following mechanism via experiments in vivo and in vitro: after PA infection in the respiratory tracts, PA3611 protein could up-regulate the expression of miR-144 and miR-642 through p38 MAPK activation in HBECs. These two microRNAs target and inhibit the IκBα gene and then activate NF-κB p65 subunit, which enhances TGF-β1 synthesis and consequently induces EMT of bronchial epithelia.