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Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction

Lookup NU author(s): Professor Christopher WardORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease. Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant.Objective: In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity.Methods: We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls. Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope). Type-IV collagen was stained to demonstrate vessels.Results: There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P < 0.001), vimentin (P < 0.001), S100A4 (P < 0.001), and fragmentation (P < 0.001), but this was less than that in large airways. Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways. Epithelial activation and S100A4 expression were related to airflow obstruction.Conclusion: EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers.

Publication metadata

Author(s): Mahmood MQ, Sohal SS, Shukla SD, Ward C, Hardikar A, Noor WD, Muller HK, Knight DA, Walters EH

Publication type: Article

Publication status: Published

Journal: International Journal of Chronic Obstructive Pulmonary Disease

Year: 2015

Volume: 10

Issue: 1

Pages: 1515-1524

Online publication date: 04/08/2015

Acceptance date: 20/04/2015

Date deposited: 31/03/2016

ISSN (print): 1176-9106

ISSN (electronic): 1178-2005

Publisher: Dove Medical Press Ltd


DOI: 10.2147/COPD.S81032


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Funder referenceFunder name
Royal Hobart Hospital Research Foundation
490023National Health and Medical Research Council