KMID : 0620920100420090606
|
|
Experimental & Molecular Medicine 2010 Volume.42 No. 9 p.606 ~ p.613
|
|
TGF-¥â1 induces mouse dendritic cells to express VEGF and its receptor (Flt-1) under hypoxic conditions
|
|
Nam Eun-Hee
Park Seok-Rae Kim Pyeung-Hyeun
|
|
Abstract
|
|
|
Angiogenesis is a multi-step process that involves the activation, proliferation, and migration of endothelial cells. We have recently shown that TGF-¥â1 can induce mouse macrophages to produce VEGF, a potent angiogenic factor. In the present study, we explored whether TGF-¥â1 has a similar effect on mouse dendritic cells. First, we show that under hypoxic conditions, TGF-¥â1 induced the expression of VEGF transcripts in bone marrow-derived dendritic cells. Overexpression of Smad3/4 further augmented TGF-¥â1-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-¥â1 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-¥â1-induced VEGF secretion in activated DC2.4 cells has wound-healing properties. Finally, Smad7 and Smurf1 negatively regulated the TGF-¥â1-induced and Smad3/4-mediated VEGF expression. Taken together, these results indicate that TGF-¥â1 can enhance the expression of VEGF and Flt-1 through the typical Smad pathway in mouse dendritic cells.
|
|
KEYWORD
|
|
dendritic cells, neovascularization, physiologic, Smad3 protein, transforming growth factor ¥â1, vascular endothelial growth factor A, vascular endothelial growth factor receptor-1
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|