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

Autor:	Jian Shen, Yan Guan, Qiang Shu, Jun-xia Jiang, Ya-nan Liu, Jian-cang Zhou, Yong-liang Jia, Qiang-min Xie, Yicheng Xie, Yun Sun, Hui-juan Shen
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Epithelial-Mesenchymal Transition Mice Transgenic Protein Tyrosine Phosphatase Non-Receptor Type 11 Vimentin Matrix metalloproteinase Cigarette Smoking Mice Pulmonary Disease Chronic Obstructive Cell Line Tumor medicine Animals Humans Epithelial–mesenchymal transition Lung cancer lcsh:RC705-779 Inhalation Exposure Lung biology Chemistry Research lcsh:Diseases of the respiratory system medicine.disease Mice Inbred C57BL medicine.anatomical_structure Matrix Metalloproteinase 9 Cell culture Cancer research biology.protein Phosphorylation Signal transduction
Zdroj:	Respiratory Research, Vol 21, Iss 1, Pp 1-14 (2020) Respiratory Research
Popis:	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 lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2b2a135e8d3c8b4f58a64f6af88dacc http://link.springer.com/article/10.1186/s12931-020-01426-9 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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