Cigarette smoke and the induction of urokinase plasminogen activator receptor in vivo: selective contribution of isoforms to bronchial epithelial phenotype

Portelli, Michael A.; Stewart, Ceri E.; Hall, Ian P.; Brightling, Christopher E.; Sayers, Ian

Abstract

The urokinase plasminogen activator receptor (uPAR) gene (PLAUR) has been identified as an asthma susceptibility gene, with polymorphisms within that gene being associated with baseline lung function, lung function decline, and lung function in a smoking population. Soluble cleaved uPAR (scuPAR), a molecule identified as a marker of increased morbidity and mortality in a number of diseases, has been shown to be elevated in the airways of patients with asthma and in patients with chronic obstructive pulmonary disease. However, the functionality of soluble receptor isoforms and their relationship with an important initiator for obstructive lung disease, cigarette smoke, remains undefined. In this study, we set out to determine the effect of cigarette smoke on soluble uPAR isoforms, its regulatory pathway and the resultant effect on bronchial epithelial cell function. We identified a positive association between cigarette pack-years and uPAR expression in the airway bronchial epithelium of biopsies from patients with asthma (n = 27; P = 0.0485). In vitro, cigarette smoke promoted cleavage of uPAR from the surface of bronchial epithelial cells (1.5× induction; P 

Citation

Portelli, M. A., Stewart, C. E., Hall, I. P., Brightling, C. E., & Sayers, I. (2015). Cigarette smoke and the induction of urokinase plasminogen activator receptor in vivo: selective contribution of isoforms to bronchial epithelial phenotype. American Journal of Respiratory Cell and Molecular Biology, 53(2), 174-183. doi:10.1165/rcmb.2014-0296oc

• Journal Article Type: Article
• Acceptance Date: Nov 19, 2014
• Online Publication Date: Dec 9, 2014
• Publication Date: Aug 31, 2015
• Deposit Date: Feb 20, 2019
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Print ISSN: 1044-1549
• Electronic ISSN: 1535-4989
• Publisher: American Thoracic Society
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Issue: 2
• Pages: 174-183
• DOI: https://doi.org/10.1165/rcmb.2014-0296oc
• Public URL: https://nottingham-repository.worktribe.com/output/1379998
• Publisher URL: https://www.atsjournals.org/doi/10.1165/rcmb.2014-0296OC