Lower respiratory tract infection due to Pseudomonas aeruginosa has become increasingly challenging, resulting in a worse morbidity and mortality. Airway remodeling is a common phenomenon in this process, to which epithelial-mesenchymal transition (EMT) may contribute as an important promoter. Previous studies showed that epithelium-specific integrin αvβ6-mediated EMT was involved in pulmonary fibrosis via transforming growth factor-β1 (TGF-β1) signaling, but whether integrin αvβ6 plays a role in the P. aeruginosa-associated airway remodeling remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) from P. aeruginosa in the presence or the absence of integrin αvβ6-blocking antibodies. Morphologic changes were observed by an inverted microscopy. The EMT markers were detected using Western blotting and immunofluorescence. The activation of TGF-β1-Smad2/3 signaling pathway was assessed. Furthermore, matrix metalloproteinase (MMP)-2 and -9 in the medium were measured using ELISA. P. aeruginosa's LPS decreased the expression of the epithelial marker E-cadherin and promoted the mesenchymal markers, vimentin and α-smooth muscle actin in BEAS-2B cells. The expression of integrin αvβ6 was significantly increased during EMT process. Blocking integrin αvβ6 could attenuate P. aeruginosa's LPS-induced EMT markers' expression via TGF-β1-Smad2/3 signaling pathway. Furthermore, blocking integrin αvβ6 could prevent morphologic changes and oversecretion of MMP-2 and -9. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of P. aeruginosa via TGF-β1-Smad2/3 signaling pathway and might be a promising therapeutic target for P. aeruginosa-associated airway remodeling.

中文翻译：

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整合素αvβ6通过TGF-β1-Smad2/ 3信号通路介导铜绿假单胞菌脂多糖诱导的人支气管上皮细胞上皮-间质转化。

铜绿假单胞菌引起的下呼吸道感染变得越来越具有挑战性，导致发病率和死亡率恶化。气道重塑是该过程中的常见现象，上皮-间质转化（EMT）可能是其中重要的促进因素。先前的研究表明，上皮特异性整合素αvβ6介导的EMT通过转化生长因子-β1（TGF-β1）信号传导参与了肺纤维化，但是整合素αvβ6是否在铜绿假单胞菌相关的气道重塑中发挥作用尚不清楚。在存在或不存在整合素αvβ6阻断抗体的情况下，将BEAS-2B细胞与铜绿假单胞菌的脂多糖（LPS）孵育。通过倒置显微镜观察形态变化。使用蛋白质印迹和免疫荧光检测EMT标记。评估了TGF-β1-Smad2/ 3信号通路的激活。此外，使用ELISA测量培养基中的基质金属蛋白酶（MMP）-2和-9。铜绿假单胞菌的LPS降低了BEAS-2B细胞上皮标记E-钙粘着蛋白的表达，并促进了间充质标记，波形蛋白和α-平滑肌肌动蛋白。在EMT过程中，整联蛋白αvβ6的表达显着增加。阻断整联蛋白αvβ6可通过TGF-β1-Smad2/ 3信号通路减弱铜绿假单胞菌LPS诱导的EMT标志物的表达。此外，阻断整联蛋白αvβ6可以阻止MMP-2和-9的形态变化和过度分泌。整合素αvβ6介导P脂多糖诱导的人支气管上皮细胞上皮-间质转化。