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

• Published in: Scientific reports Vol. 7; no. 1; pp. 10832 - 12
• Main Authors: Mahmood, Malik Quasir, Walters, Eugene Haydn, Shukla, Shakti D., Weston, Steve, Muller, Hans Konrad, Ward, Chris, Sohal, Sukhwinder Singh
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.09.2017; Nature Publishing Group
• Subjects: 631/80/86/388; 692/308/53/2421; 692/699/1785/4037; 82/1; 82/51; Airway management; beta Catenin - genetics; beta Catenin - metabolism; Biomarkers; Cadherins - genetics; Cadherins - metabolism; Chronic obstructive pulmonary disease; Cigarette smoking; Epithelial-Mesenchymal Transition - genetics; Epithelium; Fibrosis; Gene Expression; Gene Expression Regulation; Gene regulation; Health risk assessment; Humanities and Social Sciences; Humans; Immunohistochemistry; Lamina propria; Localization; Lung cancer; Mesenchyme; multidisciplinary; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Disease, Chronic Obstructive - physiopathology; Respiratory Mucosa - cytology; Respiratory Mucosa - metabolism; Respiratory tract; S100A4 protein; Science; Science (multidisciplinary); Smokers; Smoking; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Snail protein; Transcription factors; Transcription, Genetic; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11375-x

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.