Exp Mol Med.  2010 Sep;42(9):606-613. 10.3858/emm.2010.42.9.059.

TGF-beta1 induces mouse dendritic cells to express VEGF and its receptor (Flt-1) under hypoxic conditions

• Nam EH
• Park SR
• Kim PH

• KMID: 983953
• DOI: http://doi.org/10.3858/emm.2010.42.9.059

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.

Keyword

dendritic cells; neovascularization, physiologic; Smad3 protein; transforming growth factor beta1; vascular endothelial growth factor A; vascular endothelial growth factor receptor-1

MeSH Terms

Angiogenesis Inhibitors/*metabolism
Animals
Cell Line
Dendritic Cells/*metabolism
Macrophages/metabolism
Mice
Mice, Inbred BALB C
RNA, Messenger/metabolism
Signal Transduction
Smad2 Protein/metabolism
Smad3 Protein/metabolism
Smad4 Protein/metabolism
Smad7 Protein/metabolism
Transforming Growth Factor beta1/metabolism/*pharmacology
Vascular Endothelial Growth Factor A/*secretion
Vascular Endothelial Growth Factor Receptor-1/*metabolism