Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. Issue 2 (28th April 2016)

• Record Type: Journal Article
• Authors: Heijink, Irene H.; de Bruin, Harold G.; Dennebos, Robin; Jonker, Marnix R.; Noordhoek, Jacobien A.; Brandsma, Corry-Anke; van den Berge, Maarten; Postma, Dirkje S.
• Is Part Of: European respiratory journal. Volume 48:Issue 2(2016)
• Page Start: 504
• Page End: 515
• Publication Date: 2016-04-28
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.01541-2015
• Languages: English
• ISSNs: 0903-1936

Abstract

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. 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–liquid interface (ALI)-cultured PBECs. 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)-β/Smad3 signalling. In addition, WNT-5B upregulated the expression of these genes in ALI-cultured PBECs, particularly PBECs from COPD patients. Together, our results provide evidence that exaggerated WNT-5B expression upon cigarette smoke exposure in the bronchial epithelium of COPD patients leads to TGF-β/Smad3-dependent expression of genes related to airway remodelling. Cigarette smoke enhances WNT-5B expression in COPD airway epithelium, causing expression of airway remodelling genes http://ow.ly/ZxiAy