c-Abl silencing reduced the inhibitory effects of TGF-ß1 on apoptosis in systemic sclerosis dermal fibroblasts.
Mol Cell Biochem
; 405(1-2): 169-76, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25876876
ABSTRACT
It is generally accepted that the apoptosis of myofibroblasts is a crucial event in the normal wound healing. Delay in myofibroblasts apoptosis results in fibrotic diseases such as systemic sclerosis (SSc). Transforming growth factor-ß1 (TGF-ß1) is an important cytokine to induce fibroblasts differentiation into myofibroblasts. Cellular Abelson (c-Abl) is known as a TGF-ß1-modulating molecule in fibrosis. The role of c-Abl, TGF-ß1, and their interaction in SSc myofibroblasts apoptosis has not yet been fully explored. The aim of this study was to evaluate whether TGF-ß1 and inhibition of c-Abl influence Bax to Bcl-2 ratio and apoptosis in SSc and healthy dermal fibroblasts. We also would like to know whether there is interaction between TGF-ß1 and c-Abl in connection with fibroblasts apoptosis or not. Bax to Bcl-2 ratio was determined using quantitative real-time polymerase chain reaction and immunoblotting. Apoptosis was detected using annexin V and nuclear staining with Hoechst dye. Our results demonstrated that inhibition of c-Abl increased SSc and healthy dermal fibroblasts susceptibility to apoptosis through increasing in Bax to Bcl-2 mRNA and protein ratios, whereas TGF-ß1 promoted healthy fibroblasts resistance to apoptosis via decreasing Bax to Bcl-2 mRNA and protein ratios. In addition, c-Abl silencing reduced the effects of TGF-ß1 on Bax to Bcl-2 mRNA and protein ratios. These results suggested that TGF-ß1 and c-Abl individually may prevent the deletion of myofibroblasts from wounds and result in fibrosis. Results also proposed that silencing of c-Abl may promote myofibroblasts elimination from wound lesions through reduction in the TGF-ß1 inhibitory effects on apoptosis.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
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Pele
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Proteínas Proto-Oncogênicas c-abl
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Apoptose
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Fator de Crescimento Transformador beta1
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Miofibroblastos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2015
Tipo de documento:
Article