Mahmood, MQ and Reid, D and Ward, C and Muller, HK and Knight, DA and Sohal, SS and Walters, EH, Transforming growth factor (TGF) β1 and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis, Respirology, 22, (1) pp. 133-140. ISSN 1323-7799 (2017) [Refereed Article]
© 2016 Asian Pacific Society of Respirology
Background and objective: COPD is characterized by poorly reversible airflow obstruction usually due to cigarette smoking. Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of COPD, and in particular a process called epithelial mesenchymal transition (EMT), which may well be an intermediatory between smoking and both airway fibrosis and lung cancer. The downstream classical or ‘canonical’ TGF-β1 pathway is via the phosphorylated (p) Smad transcription factor system.
Methods: We have investigated TGF-β1 expression and its ‘pSmad fingerprint’ in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. A cross-sectional immunohistochemical study compared TGF-β1 and pSmad 2, 3 (excitatory) and 7 (inhibitory) expression in cells and blood vessels of three compartments of large airways: epithelium (especially the basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP).
Results: TGF-β1 expression was generally higher in COPD subjects throughout the airway wall (P < 0.01), while pSmad 2/3 expression was associated with smoking especially in current smoking COPD (P < 0.05). Expression of inhibitory pSmad 7 was also prominently reduced in patients with COPD in contrast to smokers and controls (P < 0.01). In addition, pSmad, but not TGF-β1 expression, was related to airflow obstruction and a canonical EMT biomarker (S100 A4) expression.
Conclusion: Activation of the Smad pathway in the airways is linked to EMT activity and loss of lung function. The disconnection between TGF-β1 and pSmad in terms of relationships to EMT activity and lung function suggests that factors other than or in addition to TGF-β1 are driving the process.
|Item Type:||Refereed Article|
|Keywords:||chronic obstructive pulmonary disease, epithelial mesenchymal transition, Smad 2/3, Smad 7, transforming growth factor β1|
|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)|
|Author:||Mahmood, MQ (Mr Malik Mahmood)|
|Author:||Reid, D (Dr David Reid)|
|Author:||Muller, HK (Professor Konrad Muller)|
|Author:||Sohal, SS (Dr Sukhwinder Sohal)|
|Author:||Walters, EH (Professor Haydn Walters)|
|Web of Science® Times Cited:||6|
|Deposited By:||Health Sciences|
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