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

被引:75
作者
Mahmood, Malik Quasir [1 ]
Walters, Eugene Haydn [1 ]
Shukla, Shakti D. [1 ]
Weston, Steve [1 ]
Muller, Hans Konrad [1 ]
Ward, Chris [2 ]
Sohal, Sukhwinder Singh [1 ,3 ]
机构
[1] Univ Tasmania, Sch Med, NHMRC Ctr Res Excellence Chron Resp Dis, Hobart, Tas 7000, Australia
[2] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
[3] Univ Tasmania, Fac Hlth, Sch Hlth Sci, Launceston, Tas 7248, Australia
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
英国医学研究理事会;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; SIGNALING PATHWAYS; SMOOTH-MUSCLE; ACTIVATION; MECHANISMS; COMPLEX; AIRWAYS; KINASE; GENE; VEGF;
D O I
10.1038/s41598-017-11375-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of beta-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 beta-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). beta-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, beta-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 beta-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.
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页数:12
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