Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

摘要: Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression lungs. Here, how Shp2 signaling regulates CS-induced MMP-9 production were investigated mouse lungs epithelial cell cultures (NCI-H292) found induced (increased vimentin α-SMA; decreased E-cadherin) collagen deposition tissues; cigarette extract (CSE) EMT-related phenotypes NCI-H292 cells, which partially prevented by KO/KD or inhibition. The CSE exposure suppressed Recombinant EMT, was inhibition KD/inhibition. Mechanistically, resulted ERK1/2, JNK Smad2/3 phosphorylation, KO/KD/inhibition. Consequentially, exposure-induced inhibitors. Thus, from activation Shp2/ERK1/2/JNK/Smad2/3 pathways. Our study contributes underlying mechanisms structural changes response CS, may provide novel therapeutic solutions treating associated diseases, such as COPD cancer.