Pseudomonas aeruginosa secreted protein PA3611 promotes bronchial epithelial cells epithelial-mesenchymal transition through TGF-β1 inducing p38/miRNA/NF-κB pathway
Sixia Chen, Xiaolin Chen, Shaoqing Lin, Xingran Du, Kaili Deng, Jing Wei, Yang Cao, Jiaxin Yan, Ziya
Posted 14 Oct 2020
bioRxiv DOI: 10.1101/2020.10.14.339044
Posted 14 Oct 2020
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 cells EMT caused by secreted virulence factors of PA has not been reported. In our present study, we found that PA3611 protein stimulation induced the bronchial epithelial cells EMT with 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-3065-3p and miR-6802-3p expression and p38 MAPK phosphorylation were obviously increased in bronchial epithelial cells after PA3611 stimulation, further research revealed that PA3611 promoted EMT occur through TGF-β1 induced p38/miRNA/NF-κb pathway. The function of PA3611 was also veriﬁed in PA-infected rats and results showed that △PA3611 could reduce lung inflammation and EMT. Overall, our results revealed that PA3611 promotes EMT via simulating the production of TGF-β1 induced p38/miRNA/NF-κB pathway-dependent manner, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cells EMT process and has potential use as a target for clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.
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