2005年8月
VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFR beta signaling
JOURNAL OF CELL SCIENCE
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- 巻
- 118
- 号
- 16
- 開始ページ
- 3759
- 終了ページ
- 3768
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1242/jcs.02483
- 出版者・発行元
- COMPANY OF BIOLOGISTS LTD
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 P (PDGFR,6) 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-PDGFR beta 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-PDGFR beta 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.
- リンク情報
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- DOI
- https://doi.org/10.1242/jcs.02483
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/16105884
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000231891400019&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-24944534593&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0003-1593-1855
- ID情報
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- DOI : 10.1242/jcs.02483
- ISSN : 0021-9533
- ORCIDのPut Code : 38046652
- PubMed ID : 16105884
- SCOPUS ID : 24944534593
- Web of Science ID : WOS:000231891400019