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rdf:type |
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lifeskim:mentions |
umls-concept:C0005456,
umls-concept:C0012472,
umls-concept:C0078058,
umls-concept:C0086418,
umls-concept:C0127400,
umls-concept:C0205263,
umls-concept:C0458827,
umls-concept:C0597357,
umls-concept:C0903042,
umls-concept:C1135918,
umls-concept:C1149367,
umls-concept:C1171892,
umls-concept:C1419064,
umls-concept:C1422733
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pubmed:issue |
34
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pubmed:dateCreated |
2005-8-22
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pubmed:abstractText |
Prostaglandin E2 (PGE2) can increase endothelial vascular endogrowth factor A (VEGF-A) production but the mechanisms involved are unclear. Here we characterized the transcriptional mechanisms involved in human airway smooth muscle cells (HASMC). PGE2 increased VEGF-A mRNA and protein but not mRNA stability. PGE2 stimulated the activity of a transiently transfected 2068-bp (-2018 to +50) VEGF-A promoter-driven luciferase construct. Functional 5' deletional analysis mapped the PGE2 response element to the 135-bp sequence (-85/+50) of the human VEGF-A promoter. PGE2-induced luciferase activity was reduced in cells transfected with a 135-bp VEGF promoter fragment containing mutated Sp-1 binding sites but not in cells transfected with a construct containing mutated EGR-1 binding sites. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed binding of Sp-1 to the VEGF promoter. PGE2 increased phosphorylation of Sp-1 and luciferase activity of a transfected Sp-1 reporter construct. PGE receptor agonists EP2 (ONO-AE1 259) and EP4 (ONO-AE1 329) mimicked the effect of PGE2, and reverse transcription-PCR, Western blotting, and flow cytometry confirmed the presence of EP2 and EP4 receptors. VEGF protein release and Sp-1 reporter activity were increased by forskolin and isoproterenol, which increase cytosolic cAMP, and the cAMP analogue, 8-bromoadenosine-3',5'-cyclophosphoric acid. These studies suggest that PGE2 increases VEGF transcriptionally and involves the Sp-1 binding site via a cAMP-dependent mechanism involving EP2 and EP4 receptors.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/PTGER2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGER4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, EP2...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, EP4...,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29993-30000
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15970595-Base Sequence,
pubmed-meshheading:15970595-Binding Sites,
pubmed-meshheading:15970595-Cell Survival,
pubmed-meshheading:15970595-Cells, Cultured,
pubmed-meshheading:15970595-Chromatin Immunoprecipitation,
pubmed-meshheading:15970595-Cyclic AMP,
pubmed-meshheading:15970595-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15970595-Dinoprostone,
pubmed-meshheading:15970595-Dose-Response Relationship, Drug,
pubmed-meshheading:15970595-Forskolin,
pubmed-meshheading:15970595-Gene Deletion,
pubmed-meshheading:15970595-Humans,
pubmed-meshheading:15970595-Isoproterenol,
pubmed-meshheading:15970595-Luciferases,
pubmed-meshheading:15970595-Molecular Sequence Data,
pubmed-meshheading:15970595-Mutation,
pubmed-meshheading:15970595-Myocytes, Smooth Muscle,
pubmed-meshheading:15970595-Promoter Regions, Genetic,
pubmed-meshheading:15970595-Protein Binding,
pubmed-meshheading:15970595-RNA,
pubmed-meshheading:15970595-RNA, Messenger,
pubmed-meshheading:15970595-Receptors, Prostaglandin E,
pubmed-meshheading:15970595-Receptors, Prostaglandin E, EP2 Subtype,
pubmed-meshheading:15970595-Receptors, Prostaglandin E, EP4 Subtype,
pubmed-meshheading:15970595-Sp1 Transcription Factor,
pubmed-meshheading:15970595-Time Factors,
pubmed-meshheading:15970595-Trachea,
pubmed-meshheading:15970595-Transcription, Genetic,
pubmed-meshheading:15970595-Transfection,
pubmed-meshheading:15970595-Vascular Endothelial Growth Factor A
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pubmed:year |
2005
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pubmed:articleTitle |
Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP2/EP4 receptors and SP-1 transcription factor binding sites.
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pubmed:affiliation |
Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham NG5 1PB, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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