Mahmood, MQ and Sohal, SS and Shukla, SD and Ward, C and Hardikar, A and Noor, WD and Muller, HK and Knight, DA and Walters, EH, Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction, International Journal of Chronic Obstructive Pulmonary Disease, 10 pp. 1515-1524. ISSN 1176-9106 (2015) [Refereed Article]
Copyright 2015 Mahmood et al. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) https://creativecommons.org/licenses/by-nc/3.0/
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.
|Item Type:||Refereed Article|
|Keywords:||epithelial mesenchymal transition, smoking, airflow obstruction, EMT, EGFR, S100A4, vimentin, fragmentation, small airways|
|Research Division:||Medical and Health Sciences|
|Research Group:||Cardiorespiratory Medicine and Haematology|
|Research Field:||Respiratory Diseases|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Respiratory System and Diseases (incl. Asthma)|
|UTAS Author:||Mahmood, MQ (Mr Malik Mahmood)|
|UTAS Author:||Sohal, SS (Dr Sukhwinder Sohal)|
|UTAS Author:||Shukla, SD (Mr Shakti Shukla)|
|UTAS Author:||Hardikar, A (Dr Ashutosh Hardikar)|
|UTAS Author:||Noor, WD (Dr Wan Noor)|
|UTAS Author:||Muller, HK (Professor Konrad Muller)|
|UTAS Author:||Walters, EH (Professor Haydn Walters)|
|Funding Support:||National Health and Medical Research Council (1001062)|
|Web of Science® Times Cited:||32|
|Downloads:||140 View Download Statistics|
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