Fiche publication
Date publication
mai 2015
Journal
The European respiratory journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr POLETTE Myriam
Tous les auteurs :
Gohy ST, Hupin C, Fregimilicka C, Detry BR, Bouzin C, Gaide Chevronay H, Lecocq M, Weynand B, Ladjemi MZ, Pierreux CE, Birembaut P, Polette M, Pilette C
Lien Pubmed
Résumé
In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in conducting airways. Epithelial-to-mesenchymal transition (EMT) has been recently suggested in COPD, but the mechanisms and relationship to peribronchial fibrosis remain unclear. We hypothesised that de-differentiation of the COPD respiratory epithelium through EMT could participate in airway fibrosis and thereby, in airway obstruction. Surgical lung tissue and primary broncho-epithelial cultures (in air-liquid interface (ALI)) from 104 patients were assessed for EMT markers. Cell cultures were also assayed for mesenchymal features and for the role of transforming growth factor (TGF)-β1. The bronchial epithelium from COPD patients showed increased vimentin and decreased ZO-1 and E-cadherin expression. Increased vimentin expression correlated with basement membrane thickening and airflow limitation. ALI broncho-epithelial cells from COPD patients also displayed EMT phenotype in up to 2 weeks of culture, were more spindle shaped and released more fibronectin. Targeting TGF-β1 during ALI differentiation prevented vimentin induction and fibronectin release. In COPD, the airway epithelium displays features of de-differentiation towards mesenchymal cells, which correlate with peribronchial fibrosis and airflow limitation, and which are partly due to a TGF-β1-driven epithelial reprogramming.
Mots clés
Aged, Airway Obstruction, Bronchi, cytology, Cadherins, metabolism, Cell Dedifferentiation, Epithelial Cells, cytology, Epithelial-Mesenchymal Transition, Female, Fibronectins, metabolism, Fibrosis, pathology, Gene Expression Regulation, Humans, In Vitro Techniques, Lung, pathology, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive, physiopathology, Respiratory Mucosa, metabolism, Transforming Growth Factor beta1, metabolism, Vimentin, metabolism, Zonula Occludens-1 Protein, metabolism
Référence
Eur. Respir. J.. 2015 May;45(5):1258-72
