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Transforming growth factor (TGF) β1 and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis

Mahmood, MQ ORCID: 0000-0003-1333-7940, Reid, D, Ward, C, Muller, HK, Knight, DA, Sohal, SS ORCID: 0000-0001-9627-6498 and Walters, EH ORCID: 0000-0002-0993-4374 2017 , 'Transforming growth factor (TGF) β1 and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis' , Respirology, vol. 22, no. 1 , pp. 133-140 , doi: 10.1111/resp.12882.

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Abstract

Background and objective: COPD is characterized bypoorly reversible airflow obstruction usually due to cigarettesmoking. Transforming growth factor (TGF)-β1has been implicated in the pathogenesis of COPD, andin particular a process called epithelial mesenchymaltransition (EMT), which may well be an intermediatorybetween smoking and both airway fibrosis and lungcancer. The downstream classical or ‘canonical’ TGF-β1pathway is via the phosphorylated (p) Smad transcriptionfactor system.Methods: We have investigated TGF-β1 expression andits ‘pSmad fingerprint’ in bronchoscopic airway biopsiesfrom patients with COPD, and in smoking andnon-smoking controls. A cross-sectional immunohistochemicalstudy compared TGF-β1 and pSmad 2, 3(excitatory) and 7 (inhibitory) expression in cells andblood vessels of three compartments of large airways:epithelium (especially the basal region), reticularbasement membrane (Rbm) and underlying laminapropria (LP).Results: TGF-β1 expression was generally higher inCOPD subjects throughout the airway wall (P Conclusion: Activation of the Smad pathway in the airwaysis linked to EMT activity and loss of lung function.The disconnection between TGF-β1 and pSmad in termsof relationships to EMT activity and lung function suggests that factors other than or in addition to TGF-β1are driving the process.

Item Type: Article
Authors/Creators:Mahmood, MQ and Reid, D and Ward, C and Muller, HK and Knight, DA and Sohal, SS and Walters, EH
Keywords: chronic obstructive pulmonary disease, epithelial mesenchymal transition, Smad 2/3, Smad 7, transforming growth factor β1
Journal or Publication Title: Respirology
Publisher: Blackwell Publishing Asia
ISSN: 1323-7799
DOI / ID Number: 10.1111/resp.12882
Copyright Information:

© 2016 Asian Pacific Society of Respirology

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