PT  - JOURNAL ARTICLE
AU  - Irene H. Heijink
AU  - Harold G. de Bruin
AU  - Robin Dennebos
AU  - Marnix R. Jonker
AU  - Jacobien A. Noordhoek
AU  - Corry-Anke Brandsma
AU  - Maarten van den Berge
AU  - Dirkje S. Postma
TI  - Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD
AID  - 10.1183/13993003.01541-2015
DP  - 2016 Aug 01
TA  - European Respiratory Journal
PG  - 504--515
VI  - 48
IP  - 2
4099  - http://erj.ersjournals.com/content/48/2/504.short
4100  - http://erj.ersjournals.com/content/48/2/504.full
SO  - Eur Respir J2016 Aug 01; 48
AB  - 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