Malik Q Mahmood1, David Reid2, Chris Ward3, Hans K Muller1, Darryl A Knight4, Sukhwinder S Sohal1,5, Eugene H Walters1. 1. NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. 2. Queensland Institute of Medical Research, Iron Metabolism Laboratory, Brisbane, Queensland, Australia. 3. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. 4. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia. 5. Faculty of Health, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
Abstract
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.
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.
Authors: Angela Koutsokera; Pierre J Royer; Jean P Antonietti; Andreas Fritz; Christian Benden; John D Aubert; Adrien Tissot; Karine Botturi; Antoine Roux; Martine L Reynaud-Gaubert; Romain Kessler; Claire Dromer; Sacha Mussot; Hervé Mal; Jean-François Mornex; Romain Guillemain; Christiane Knoop; Marcel Dahan; Paola M Soccal; Johanna Claustre; Edouard Sage; Carine Gomez; Antoine Magnan; Christophe Pison; Laurent P Nicod Journal: Front Med (Lausanne) Date: 2017-07-17
Authors: Joanna Wieczfinska; Tomasz Kowalczyk; Przemyslaw Sitarek; Ewa Skała; Rafal Pawliczak Journal: Int J Environ Res Public Health Date: 2018-05-18 Impact factor: 3.390
Authors: Malik Quasir Mahmood; Eugene Haydn Walters; Shakti D Shukla; Steve Weston; Hans Konrad Muller; Chris Ward; Sukhwinder Singh Sohal Journal: Sci Rep Date: 2017-09-07 Impact factor: 4.379