Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-1-31
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
404
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
997-1003
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
NF-?B suppresses HIF-1? response by competing for P300 binding.
pubmed:affiliation
Universidade Católica de Brasília, Pós-Graduação em Ciências Genômicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasília, DF, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural