{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:01:58Z","timestamp":1791248518432,"version":"4.1.0"},"reference-count":37,"publisher":"European Respiratory Society (ERS)","issue":"2","funder":[{"DOI":"10.13039\/501100006006","name":"ICIN Netherlands Heart Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2016,3,10]]},"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Wingless\/integrase-1 (WNT) signalling is associated with lung inflammation and repair, but its role in chronic obstructive pulmonary disease (COPD) pathogenesis is unclear. We investigated whether cigarette smoke-induced dysregulation of WNT-5B contributes to airway remodelling in COPD.<\/jats:p><jats:p>We analysed WNT-5B protein expression in the lung tissue of COPD patients and (non)smoking controls, and investigated the effects of cigarette smoke exposure on WNT-5B expression in COPD and control-derived primary bronchial epithelial cells (PBECs). Additionally, we studied downstream effects of WNT-5B on remodelling related genes fibronectin, matrix metalloproteinase (MMP)-2, MMP-9 and SnaiI in BEAS-2B and air\u2013liquid interface (ALI)-cultured PBECs.<\/jats:p><jats:p>We observed that airway epithelial WNT-5B expression is significantly higher in lung tissue from COPD patients than controls. Cigarette smoke extract significantly increased mRNA expression of WNT-5B in COPD, but not control-derived PBECs. Exogenously added WNT-5B augmented the expression of remodelling related genes in BEAS-2B cells, which was mediated by transforming growth factor (TGF)-\u03b2\/Smad3 signalling. In addition, WNT-5B upregulated the expression of these genes in ALI-cultured PBECs, particularly PBECs from COPD patients.<\/jats:p><jats:p>Together, our results provide evidence that exaggerated WNT-5B expression upon cigarette smoke exposure in the bronchial epithelium of COPD patients leads to TGF-\u03b2\/Smad3-dependent expression of genes related to airway remodelling.<\/jats:p>","DOI":"10.1183\/13993003.01541-2015","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T05:43:56Z","timestamp":1461908636000},"page":"504-515","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":64,"title":["Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD"],"prefix":"10.1183","volume":"48","author":[{"given":"Irene H.","family":"Heijink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold G.","family":"de 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