FGF regulates TGF-ß signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression.
Cell Rep
; 2(6): 1684-96, 2012 Dec 27.
Article
em En
| MEDLINE
| ID: mdl-23200853
ABSTRACT
Maintenance of normal endothelial function is critical to various aspects of blood vessel function, but its regulation is poorly understood. In this study, we show that disruption of baseline fibroblast growth factor (FGF) signaling to the endothelium leads to a dramatic reduction in let-7 miRNA levels that, in turn, increases expression of transforming growth factor (TGF)-ß ligands and receptors and activation of TGF-ß signaling, leading to endothelial-to-mesenchymal transition (Endo-MT). We also find that Endo-MT is an important driver of neointima formation in a murine transplant arteriopathy model and in rejection of human transplant lesions. The decline in endothelial FGF signaling input is due to the appearance of an FGF resistance state that is characterized by inflammation-dependent reduction in expression and activation of key components of the FGF signaling cascade. These results establish FGF signaling as a critical factor in maintenance of endothelial homeostasis and point to an unexpected role of Endo-MT in vascular pathology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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MicroRNAs
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Endotélio
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Neointima
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Fatores de Crescimento de Fibroblastos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article