Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-11-1
pubmed:abstractText
Adenosine has been widely associated with hypoxia of many origins, including those associated with inflammation and tumorogenesis. A number of recent studies have implicated metabolic control of adenosine generation at sites of tissue hypoxia. Here, we examine adenosine receptor control and amplification of signaling through transcriptional regulation of endothelial and epithelial adenosine receptors. Initial studies confirmed previous findings indicating selective induction of human adenosine A2B receptor (A2BR) by hypoxia. Analysis of the cloned human A2BR promoter identified a functional hypoxia-responsive region, including a functional binding site for hypoxia-inducible factor (HIF) within the A2BR promoter. Further studies examining HIF-1alpha DNA binding and HIF-1alpha gain and loss of function confirmed strong dependence of A2BR induction by HIF-1alpha in vitro and in vivo mouse models. Additional studies in endothelia overexpressing full-length A2BR revealed functional phenotypes of increased barrier function and enhanced angiogenesis. Taken together, these results demonstrate transcriptional coordination of A2BR by HIF-1alpha and amplified adenosine signaling during hypoxia. These findings may provide an important link between hypoxia and metabolic conditions associated with inflammation and angiogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2242-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17077301-Base Sequence, pubmed-meshheading:17077301-Cell Hypoxia, pubmed-meshheading:17077301-Cell Line, pubmed-meshheading:17077301-Cells, Cultured, pubmed-meshheading:17077301-Chromatin, pubmed-meshheading:17077301-Cloning, Molecular, pubmed-meshheading:17077301-DNA Primers, pubmed-meshheading:17077301-Endothelium, Vascular, pubmed-meshheading:17077301-Humans, pubmed-meshheading:17077301-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:17077301-Intestinal Mucosa, pubmed-meshheading:17077301-Molecular Sequence Data, pubmed-meshheading:17077301-Neovascularization, Physiologic, pubmed-meshheading:17077301-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17077301-Phenotype, pubmed-meshheading:17077301-Promoter Regions, Genetic, pubmed-meshheading:17077301-RNA, Small Interfering, pubmed-meshheading:17077301-Receptor, Adenosine A2B
pubmed:year
2006
pubmed:articleTitle
HIF-dependent induction of adenosine A2B receptor in hypoxia.
pubmed:affiliation
Center for Experimental Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural