{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:18:25Z","timestamp":1782706705495,"version":"3.54.5"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2009=\u200927; P\u2009=\u20090.0485). In vitro, cigarette smoke promoted cleavage of uPAR from the surface of bronchial epithelial cells (1.5\u00d7 induction; P\u2009&amp;lt;\u20090.0001) and induced the soluble spliced isoform through changes in messenger RNA expression (\u223c2\u00d7 change; P\u2009&amp;lt;\u20090.001), driven by loss of endogenous 3\u2032 untranslated region suppression. Elevated expression of the soluble isoforms resulted in a proremodeling cell phenotype, characterized by increased proliferation and matrix metalloproteinase-9 expression in primary bronchial epithelial cells. This suggests that cigarette smoke elevates soluble receptor isoforms in bronchial epithelial cells through direct (cleavage) and indirect (messenger RNA expression) means. These findings provide further insight into how cigarette smoke may influence changes in the airways of importance to airway remodeling and obstructive lung disease progression.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0296oc","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T11:08:39Z","timestamp":1418123319000},"page":"174-183","source":"Crossref","is-referenced-by-count":7,"title":["Cigarette Smoke and the Induction of Urokinase Plasminogen Activator Receptor\n                    <i>In Vivo<\/i>\n                    : Selective Contribution of Isoforms to Bronchial Epithelial Phenotype"],"prefix":"10.1093","volume":"53","author":[{"given":"Michael A.","family":"Portelli","sequence":"first","affiliation":[{"name":"Division of Respiratory Medicine, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceri E.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.","family":"Hall","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[{"name":"Department of Infection, Inflammation and Immunity, Institute for Lung Health, University of Leicester, Leicester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Sayers","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, University of Nottingham, Queen\u2019s Medical Centre, Nottingham, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2026021122333281600_bib1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1165\/rcmb.2006-0040OC","article-title":"Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells","volume":"35","author":"Chu","year":"2006","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021122333281600_bib2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1136\/thoraxjnl-2011-200508","article-title":"uPAR regulates bronchial epithelial repair in vitro and is elevated in asthmatic epithelium","volume":"67","author":"Stewart","year":"2012","journal-title":"Thorax"},{"key":"2026021122333281600_bib3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1164\/rccm.200703-390OC","article-title":"Gene expression profiling in patients with chronic obstructive pulmonary disease and lung 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