RT Journal Article
SR Electronic
T1 LSC 2014 abstract - Epithelial to mesenchymal transition in the airway epithelium from COPD patients: Correlation to disease severity
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3892
VO 44
IS Suppl 58
A1 Sophie Gohy
A1 Bruno Detry
A1 Myriam Polette
A1 Chantal Fregimilika
A1 Caroline Bouzin
A1 Héloïse Gaide Chevronay
A1 Chirstophe Pierreux
A1 Cloé Hupin
A1 Birgit Weynand
A1 Maha Ladjemi
A1 Charles Pilette
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P3892.abstract
AB Rationale: In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in the airways. Epithelial to mesenchymal transition (EMT) has been suggested in COPD, mainly in alveolar epithelial cells.Objectives: To evaluate the presence of EMT in the airways and primary air-liquid interface cultures of bronchial epithelial cells (ALI-HBEC) from COPD patients.Methods: Surgical lung tissue of COPD and control patients (n=49) and ALI-HBEC cultures (n=57) were assessed for EMT markers by immunohistochemistry, western blot and real-time qPCR. Mesenchymal functionalities of ALI-HBEC were assayed through fibronectin release and wound repair.Results: The bronchial epithelium from COPD patients, as compared to non-smoker controls, showed increased vimentin expression in large and small airways and correlated with airway obstruction (FEV1, FEV1/VC ratio and DLCO). In addition, epithelial E-cadherin and zonula occludens-1 (ZO-1) were decreased in large airways. Increased epithelial vimentin expression correlated to subepithelial deposition and basement membrane thickness in COPD thick slices. The COPD bronchial epithelium displayed similar features in vitro and correlated also to lung function. Moreover, COPD ALI-HBEC showed mesenchymal functions such as extra-cellular production of fibronectin and impaired migration during wound repair.Conclusions: The bronchial epithelium from COPD patients displays EMT features in lung tissue, which correlates to disease severity and which are recapitulated in primary cultures in ALI conditions. We propose that this abnormal epithelial programming contributes to peribronchial fibrosis in COPD.