• Malik Q Mahmood, David Reid, Chris Ward, Hans K Muller, Darryl A Knight, Sukhwinder S Sohal, and Eugene H Walters.
• NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
• Respirology. 2017 Jan 1; 22 (1): 133-140.

Background And ObjectiveCOPD 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.MethodsWe 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).ResultsTGF-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.ConclusionActivation 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.© 2016 Asian Pacific Society of Respirology.

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