Source:http://linkedlifedata.com/resource/pubmed/id/18500250
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2008-6-24
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pubmed:abstractText |
Hypoxia-inducible factor-1 (HIF-1) plays a central role in cellular response to hypoxia by activating vascular endothelial growth factor (VEGF) and other angiogenic factors. Prolyl hydroxylase domain-2 (PHD2) protein induces the degradation of HIF-1 by hydroxylating specific prolyl residues. Therefore gene silencing of PHD2 by RNA interference (RNAi) might increase the expression of angiogenic growth factors and, consequently, neoangiogenesis through the stabilization of HIF-1alpha. In this study we have shown that the specific silencing of PHD2 is sufficient for stabilizing HIF-1alpha and increasing its transcriptional activity, resulting in the increased expression of angiogenic factors including VEGF and fibroblast growth factor-2 (FGF2). Moreover, when PHD2-siRNA vector was used, the increase in VEGF secretion was observed for as long as 18 days after transfection. In vitro treatment of human umbilical vein endothelical cells with conditioned medium from PHD2-siRNA vector-transfected NIH3T3 cells was shown to increase cell proliferation. Also, in vivo angiogenesis was observed in mice implanted with Matrigel plugs mixed with NIH3T3 cells transfected with PHD2-siRNA vector. These results indicate that PHD2 silencing induces expressions of multiple angiogenic growth factors by stabilizing HIF-1alpha, and that the implantation of cells transfected with PHD2-siRNA vector is sufficient to enhance angiogenesis in vivo. In the light of these findings, PHD2 silencing by RNAi might offer a potential tool for angiogenic therapy.
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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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Egln1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Procollagen-Proline Dioxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1525-0024
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1227-34
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18500250-Animals,
pubmed-meshheading:18500250-Cell Proliferation,
pubmed-meshheading:18500250-DNA-Binding Proteins,
pubmed-meshheading:18500250-Female,
pubmed-meshheading:18500250-Gene Expression Regulation,
pubmed-meshheading:18500250-Gene Therapy,
pubmed-meshheading:18500250-Humans,
pubmed-meshheading:18500250-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:18500250-Immediate-Early Proteins,
pubmed-meshheading:18500250-Mice,
pubmed-meshheading:18500250-Mice, Inbred BALB C,
pubmed-meshheading:18500250-NIH 3T3 Cells,
pubmed-meshheading:18500250-Neovascularization, Physiologic,
pubmed-meshheading:18500250-Procollagen-Proline Dioxygenase,
pubmed-meshheading:18500250-RNA, Small Interfering,
pubmed-meshheading:18500250-RNA Interference,
pubmed-meshheading:18500250-Vascular Endothelial Growth Factor A
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pubmed:year |
2008
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pubmed:articleTitle |
Enhancement of angiogenesis through stabilization of hypoxia-inducible factor-1 by silencing prolyl hydroxylase domain-2 gene.
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pubmed:affiliation |
Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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