TY - JOUR
T1 - Cigarette smoke-induced epithelial expression of WNT-5B
T2 - implications for COPD
AU - Heijink, Irene H.
AU - de Bruin, Harold G.
AU - Dennebos, Robin
AU - Jonker, Marnix R.
AU - Noordhoek, Jacobien A.
AU - Brandsma, Corry-Anke
AU - van den Berge, Maarten
AU - Postma, Dirkje S.
N1 - Copyright ©ERS 2016.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
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)-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.
KW - OBSTRUCTIVE PULMONARY-DISEASE
KW - MESENCHYMAL TRANSITION
KW - AIRWAY EPITHELIUM
KW - TRANSFORMING GROWTH-FACTOR-BETA-1
KW - BETA ACTIVATION
KW - CELLS
KW - FIBROSIS
KW - LUNG
KW - MATRIX-METALLOPROTEINASE-9
KW - PROGRESSION
U2 - 10.1183/13993003.01541-2015
DO - 10.1183/13993003.01541-2015
M3 - Article
C2 - 27126693
SN - 0903-1936
VL - 48
SP - 504
EP - 515
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
ER -