TGF-beta1 induces mouse dendritic cells to express VEGF and its receptor (Flt-1) under hypoxic conditions.
10.3858/emm.2010.42.9.059
- Author:
Eun Hee NAM
1
;
Seok Rae PARK
;
Pyeung Hyeun KIM
Author Information
1. Department of Molecular Bioscience, College of Biomedical Sciences, Kangwon National University, Chuncheon 200-701, Korea. phkim@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
dendritic cells;
neovascularization, physiologic;
Smad3 protein;
transforming growth factor beta1;
vascular endothelial growth factor A;
vascular endothelial growth factor receptor-1
- MeSH:
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
- From:Experimental & Molecular Medicine
2010;42(9):606-613
- CountryRepublic of Korea
- Language:English
-
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.
