Transforming growth factor-ß1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma.
Mol Med Rep
; 8(6): 1663-8, 2013 12.
Article
em En
| MEDLINE
| ID: mdl-24126595
ABSTRACT
Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and an increase in mucous glands, which may lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we observed substantially thickened lung tissue with extensive fibrosis in ovalbumin-sensitized mice, which was interrelated with transforming growth factor-ß1 (TGF-ß1) expression in bronchoalveolar lavage fluid. In vitro experiments further demonstrated that TGF-ß1 resulted in epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, which was characterized by the expected decrease in E-cadherin expression and the increase in vimentin and α-smooth muscle actin expression, as well as the associated increase in Snail expression at mRNA and protein levels. Furthermore, the downregulation of Snail by small interfering RNA (siRNA) attenuated the TGF-ß1induced EMT-like phenotype. Of note, a significantly increased synthesis of fibronectin was observed following TGF-ß1 treatment, which further supported the hypothesis that EMT is a pivotal factor in peribronchial fibrosis. In combination, the results indicated that myofibroblasts deriving from bronchial epithelial cells via EMT may contribute to peribronchial fibrosis and that Snail may be an important factor in this phenomenon.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Asma
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Fatores de Transcrição
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Brônquios
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Células Epiteliais
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Fator de Crescimento Transformador beta1
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Remodelação das Vias Aéreas
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Transição Epitelial-Mesenquimal
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article