Source:http://linkedlifedata.com/resource/pubmed/id/21187066
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-1-31
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pubmed:abstractText |
Hypoxia has emerged as a key determinant of osteogenesis. HIF-1? is the transcription factor mediating hypoxia responses that include induction of VEGF and related bone induction. Inflammatory signals antagonize bone repair via the NF-?B pathway. The present investigation explored the functional relationship of hypoxia (HIF-1? function) and inflammatory signaling (NF-?B) in stem like and osteoprogenitor cell lines. The potential interaction between HIF-1? and NF-?B signaling was explored by co-transfection studies in hFOB with p65, HIF-1? and 9x-HRE-luc or HIF-1? target genes reporter plasmids. Nuclear cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and confirmed by co-immunoprecipitation/western blotting assays. The results show that inflammatory stimulation (TNF-? treatment) causes a marked inhibition of HIF-1? function at the HRE in all cell lines studied. Also, co-transfection with p65 expression vector leads to reduced hVEGFp transcription after DFO-induced hypoxia. However, TNF-? treatment had little effect on HIF-1? mRNA levels. The functional interaction of Gal4-HIF-1? and VP16-p300 fusion proteins is effectively blocked by expression of p65 in a dose dependent manner. It was concluded that NF-?B-mediated inflammatory signaling is able to block HIF-1? transactivation at HRE-encoding genes by direct competition for p300 binding at the promoter. Inflammation may influence the stem cell niche and tissue regeneration by influencing cellular responses to hypoxia.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/EP300 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1090-2104
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
404
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
997-1003
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:21187066-Cell Hypoxia,
pubmed-meshheading:21187066-Cell Line,
pubmed-meshheading:21187066-E1A-Associated p300 Protein,
pubmed-meshheading:21187066-Gene Expression,
pubmed-meshheading:21187066-Humans,
pubmed-meshheading:21187066-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:21187066-Inflammation,
pubmed-meshheading:21187066-NF-kappa B,
pubmed-meshheading:21187066-Nitric Oxide Synthase Type II,
pubmed-meshheading:21187066-Osteogenesis,
pubmed-meshheading:21187066-Promoter Regions, Genetic,
pubmed-meshheading:21187066-RNA, Messenger,
pubmed-meshheading:21187066-Transcription Factor RelA,
pubmed-meshheading:21187066-Transcriptional Activation,
pubmed-meshheading:21187066-Vascular Endothelial Growth Factor A
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pubmed:year |
2011
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pubmed:articleTitle |
NF-?B suppresses HIF-1? response by competing for P300 binding.
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pubmed:affiliation |
Universidade Católica de Brasília, Pós-Graduação em Ciências Genômicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasília, DF, Brazil.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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