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β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction

Citation

Mahmood, MQ and Walters, EH and Shukla, SD and Weston, S and Muller, HK and Ward, C and Sohal, SS, β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction, Scientific Reports, 7, (1) Article 10832. ISSN 2045-2322 (2017) [Refereed Article]


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Copyright 2017 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41598-017-11375-x

Abstract

COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their "cellular localization" in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01). Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05). In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4). The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction.

Item Details

Item Type:Refereed Article
Keywords:COPD, lung cancer
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
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:Walters, EH (Professor Haydn Walters)
UTAS Author:Shukla, SD (Mr Shakti Shukla)
UTAS Author:Weston, S (Mr Steven Weston)
UTAS Author:Muller, HK (Professor Konrad Muller)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:121246
Year Published:2017
Web of Science® Times Cited:15
Deposited By:Health Sciences
Deposited On:2017-09-19
Last Modified:2018-09-13
Downloads:31 View Download Statistics

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