Transforming growth factor (TGF) ß1 and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis.
Respirology
; 22(1): 133-140, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27614607
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença Pulmonar Obstrutiva Crônica
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Proteína Smad2
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Fator de Crescimento Transformador beta1
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Transição Epitelial-Mesenquimal
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Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prevalence_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Respirology
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Austrália