Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD

Irene H. Heijink*, Harold G. de Bruin, Robin Dennebos, Marnix R. Jonker, Jacobien A. Noordhoek, Corry-Anke Brandsma, Maarten van den Berge, Dirkje S. Postma

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

41 Citaten (Scopus)

Samenvatting

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)-beta/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-beta/Smad3-dependent expression of genes related to airway remodelling.

Originele taal-2English
Pagina's (van-tot)504-515
Aantal pagina's12
TijdschriftEuropean Respiratory Journal
Volume48
Nummer van het tijdschrift2
DOI's
StatusPublished - 1-aug-2016

Citeer dit