Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition.

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.

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Gohy, S., Hupin, C., Fregimilicka, C., Detry, B., Bouzin, C., Gaide Chevronnay, H. P., Lecocq, M., Weynand, B., Ladjemi, M., Pierreux, C., Birembaut, P., Polette, M., & Pilette, C. (2015). Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition. The European Respiratory Journal, 45(5), 1258-1272. https://doi.org/10.1183/09031936.00135814 (Original work published 2015)