- Title
- Transforming growth factor (TGF) β₁ and Smad signalling pathways: a likely key to EMT-associated COPD pathogenesis
- Creator
- Mahmood, Malik Q.; Reid, David; Ward, Chris; Muller, Hans K.; Knight, Darryl A.; Sohal, Sukhwinder S.; Walters, Eugene H.
- Relation
- Funding BodyNHMRCGrant Number1001062 http://purl.org/au-research/grants/nhmrc/1001062
- Relation
- Respirology Vol. 22, Issue 1, p. 133-140
- Publisher Link
- http://dx.doi.org/10.1111/resp.12882
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2017
- Description
- Background and objective: COPD is characterized by poorly reversible airflow obstruction usually due to cigarette smoking. Transforming growth factor (TGF)-ß1 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-ß1 pathway is via the phosphorylated (p) Smad transcription factor system. Methods: We have investigated TGF-ß1 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-ß1 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-ß1 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-ß1 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-ß1 and pSmad in terms of relationships to EMT activity and lung function suggests that factors other than or in addition to TGF-ß1 are driving the process.
- Subject
- chronic obstructive pulmonary disease; epithelial mesenchymal transition; Smad 2/3; Smad 7; transforming growth factor β1
- Identifier
- http://hdl.handle.net/1959.13/1391808
- Identifier
- uon:33298
- Identifier
- ISSN:1323-7799
- Language
- eng
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