Apolipoprotein A1 Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells / 결핵및호흡기질환
Tuberculosis and Respiratory Diseases
; : 143-152, 2016.
Article
em En
| WPRIM
| ID: wpr-197492
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action. METHODS: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. RESULTS: TGF-β1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1-induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. CONCLUSION: Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Apolipoproteínas
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Fenótipo
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Fosforilação
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Proteínas Quinases
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Fibrose Pulmonar
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Fibrose
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Camundongos Transgênicos
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Fatores de Crescimento Transformadores
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Caderinas
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Actinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Tuberculosis and Respiratory Diseases
Ano de publicação:
2016
Tipo de documento:
Article