TGF-beta1 induces mouse dendritic cells to express VEGF and its receptor (Flt-1) under hypoxic conditions
Experimental & Molecular Medicine
; : 606-613, 2010.
Article
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| WPRIM
| ID: wpr-162256
Biblioteca responsable:
WPRO
ABSTRACT
Angiogenesis is a multi-step process that involves the activation, proliferation, and migration of endothelial cells. We have recently shown that TGF-beta1 can induce mouse macrophages to produce VEGF, a potent angiogenic factor. In the present study, we explored whether TGF-beta1 has a similar effect on mouse dendritic cells. First, we show that under hypoxic conditions, TGF-beta1 induced the expression of VEGF transcripts in bone marrow-derived dendritic cells. Overexpression of Smad3/4 further augmented TGF-beta1-induced VEGF transcription, while overexpression of DN-Smad3 decreased VEGF transcription in DC2.4 cells, a mouse dendritic cell line. We also show that TGF-beta1 and Smads are involved in the induction of VEGF protein secretion. Interestingly, under the same conditions, the expression of VEGF receptor 1 (Flt-1) was also elevated at both the transcriptional and protein levels. Additionally, we found that the TGF-beta1-induced VEGF secretion in activated DC2.4 cells has wound-healing properties. Finally, Smad7 and Smurf1 negatively regulated the TGF-beta1-induced and Smad3/4-mediated VEGF expression. Taken together, these results indicate that TGF-beta1 can enhance the expression of VEGF and Flt-1 through the typical Smad pathway in mouse dendritic cells.
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Texto completo:
1
Índice:
WPRIM
Asunto principal:
Células Dendríticas
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ARN Mensajero
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Transducción de Señal
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Línea Celular
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Inhibidores de la Angiogénesis
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Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Factor A de Crecimiento Endotelial Vascular
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Proteína smad7
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Proteína Smad2
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Proteína smad3
Límite:
Animals
Idioma:
En
Revista:
Experimental & Molecular Medicine
Año:
2010
Tipo del documento:
Article