Source:http://linkedlifedata.com/resource/pubmed/id/16105884
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
Pt 16
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| pubmed:dateCreated |
2005-8-17
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| pubmed:abstractText |
Combined stimulation with VEGF-A, FGF-2, or PDGF-BB has emerged as a potent strategy for therapeutic angiogenesis, although the mechanisms underlying the synergism of these factors are not well understood. In the present study, we investigated the mechanism of synergism between VEGF-A and FGF-2 by using Matrigel plug assay in vivo and embryonic stem cell (ESC)-derived VEGF receptor 2 (VEGFR2)-positive cells in vitro. Experiments in vitro revealed that, in addition to having direct mitogenic effects, these molecules enhance intercellular PDGF-B signaling in a cell-type specific manner: VEGF-A enhances endothelial PDGF-B expression, whereas FGF-2 enhances mural PDGF receptor beta (PDGFRbeta) expression. Co-stimulation with VEGF-A and FGF-2 caused significant mural cell recruitment in vitro and formation of functional neovasculature in vivo, compared with single-agent stimulation. These effects were abrogated not only by anti-PDGFRbeta neutralizing antibody, but also by exogenous PDGF-BB, which could overwhelm the endogenous PDGF-BB distribution. These findings indicated the importance of preservation of the periendothelial PDGF-BB gradient. Thus, we demonstrated that the directional enhancement of endogenous PDGF-B-PDGFRbeta signaling is indispensable for the synergistic effect of VEGF-A and FGF-2 on neoangiogenesis in adults. The findings provide insights into the mechanisms underlying the effects of co-stimulation by growth factors, which could lead to rational design of therapeutic angiogenic strategies.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-sis,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/vascular endothelial growth factor...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0021-9533
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
|
| pubmed:volume |
118
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3759-68
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16105884-Animals,
pubmed-meshheading:16105884-Antibodies,
pubmed-meshheading:16105884-Blood Vessels,
pubmed-meshheading:16105884-Cell Communication,
pubmed-meshheading:16105884-Cell Differentiation,
pubmed-meshheading:16105884-Cell Line,
pubmed-meshheading:16105884-Drug Synergism,
pubmed-meshheading:16105884-Endothelial Cells,
pubmed-meshheading:16105884-Fibroblast Growth Factor 2,
pubmed-meshheading:16105884-Male,
pubmed-meshheading:16105884-Mice,
pubmed-meshheading:16105884-Mice, Inbred ICR,
pubmed-meshheading:16105884-Neovascularization, Physiologic,
pubmed-meshheading:16105884-Proto-Oncogene Proteins c-sis,
pubmed-meshheading:16105884-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:16105884-Signal Transduction,
pubmed-meshheading:16105884-Up-Regulation,
pubmed-meshheading:16105884-Vascular Endothelial Growth Factor A
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| pubmed:year |
2005
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| pubmed:articleTitle |
VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling.
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| pubmed:affiliation |
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo 113-0033, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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