title: Involvement of urokinase in cigarette smoke extract-induced epithelial-mesenchymal transition in human small airway epithelial cells.
abstract: Urokinase-type plasminogen activator (uPA) augments inflammation and tissue remodeling during lung injury and repair. The uPA expression in small airway epithelium of chronic obstructive pulmonary disease (COPD) increases. Epithelial-mesenchymal transition (EMT) is important in the small airway fibrosis of COPD. This study shows the uPA regulation in cigarette smoke extract (CSE)-induced EMT in human small airway epithelial cell lines (HSAEpiCs). uPA is overexpressed in the small airway epithelium of COPD patients and CSE-treated cell lines. Furthermore, uPA expression correlated with vimentin expression in the small airway epithelium of COPD patients. uPA inhibition blocks CSE-induced EMT by reversing E-cadherin and α-catenin expression and retarding the induction of N-cadherin and vimentin, resulting in reduction in migration. uPA overexpression in HSAEpiC cells also promotes EMT and migration. EMT is partly reversed in uPA-overexpressing HSAEpiC cells through the silencing expression of uPA receptor. In conclusion, this study provides new insights into the contribution of uPA upregulation to EMT associated with small airway remodeling in COPD.
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1] Department of Anatomy, Shandong University School of Medicine, Jinan, China [2] School of Ocean, Shandong University, Weihai, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yuke
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000378:metabolism; D014026:Nicotiana; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012906:Smoke; D014746:Vimentin; D014568:Urokinase-Type Plasminogen Activator