Echistatin/BYL-719 impedes epithelial-mesenchymal transition in pulmonary fibrosis induced by silica through modulation of the Integrin ß1/ILK/PI3K signaling pathway.
Int Immunopharmacol
; 136: 112368, 2024 Jul 30.
Article
em En
| MEDLINE
| ID: mdl-38823175
ABSTRACT
Silicosis is a chronic fibroproliferative lung disease caused by long-term inhalation of crystalline silica dust, characterized by the proliferation of fibroblasts and pulmonary interstitial fibrosis. Currently, there are no effective treatments available. Recent research suggests that the Integrin ß1/ILK/PI3K signaling pathway may be associated with the pathogenesis of silicosis fibrosis. In this study, we investigated the effects of Echistatin (Integrin ß1 inhibitor) and BYL-719 (PI3K inhibitor) on silicosis rats at 28 and 56 days after silica exposure. Histopathological analysis of rat lung tissue was performed using H&E staining and Masson staining. Immunohistochemistry, Western blotting, and qRT-PCR were employed to assess the expression of markers associated with epithelial-mesenchymal transition (EMT), fibrosis, and the Integrin ß1/ILK/PI3K pathway in lung tissue. The results showed that Echistatin, BYL 719 or their combination up-regulated the expression of E-cadherin and down-regulated the expression of Vimentin and extracellular matrix (ECM) components, including type I and type III collagen. The increase of Snail, AKT and ß-catenin in the downstream Integrin ß1/ILK/PI3K pathway was inhibited. These results indicate that Echistatin and BYL 719 can inhibit EMT and pulmonary fibrosis by blocking different stages of Integrinß1 /ILK/PI3K signaling pathway. This indicates that the Integrin ß1/ILK/PI3K signaling pathway is associated with silica-induced EMT and may serve as a potential therapeutic target for silicosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
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Silicose
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Transdução de Sinais
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Proteínas Serina-Treonina Quinases
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Dióxido de Silício
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Integrina beta1
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Fosfatidilinositol 3-Quinases
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Transição Epitelial-Mesenquimal
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article