Epithelial mesenchymal transition (EMT) in small and large airways of smokers; and relation to airflow obstruction

Abstract

Background: We previously reported that EMT is an active process in the large airways of smokers and patients with COPD. Objective: In this study we have investigated EMT biomarkers expression in small airways (SAs) compared to large airways (LAs) in subjects with chronic airflow limitation (CAL), and type of EMT, on the basis of vascularity. Methods: We evaluated Rbm fragmentation (core structural marker of EMT) and EMT-related mesenchymal biomarkers in SAs and LAs from resected lung tissue from 18 subjects with CAL and, 9 normal controls using immunohistochemistry. Tissues were stained for vimentin and N-cadherin (mesenchymal marker), S100A4 (fibroblast epitope). Epidermal growth factor receptor (EGFR) as a marker of epithelial activation and type-IV collagen for vessels. Results: There was significantly increased expression of EMT-related markers in SAs compared to control tissue: Rbm fragmentation (p Conclusions: EMT is active in SAs and related to small airway obstruction. We suggest that airway fibrosis is secondary to Type-2-EMT which is active in that compartment; in contrast Type-3-EMT is marked in LAs and may have implications for airway cancer.