Source:http://linkedlifedata.com/resource/pubmed/id/21460241
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2011-7-22
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| pubmed:abstractText |
The opioid system (opioid peptides and receptors) regulates a variety of neurophysiologic functions, including pain control. Here we show novel roles of the ? opioid system in vascular development. Previously, we revealed that cAMP/protein kinase A (PKA) signaling enhanced differentiation of vascular progenitors expressing VEGF receptor-2 (fetal liver kinase 1; Flk1) into endothelial cells (ECs) through dual up-regulation of Flk1 and Neuropilin1 (NRP1), which form a selective and sensitive VEGF(164) receptor. Kappa opioid receptor (KOR), an inhibitory G protein-coupled receptor, was highly expressed in embryonic stem cell-derived Flk1(+) vascular progenitors. The addition of KOR agonists to Flk1(+) vascular progenitors inhibited EC differentiation and 3-dimensional vascular formation. Activation of KOR decreased expression of Flk1 and NRP1 in vascular progenitors. The inhibitory effects of KOR were reversed by 8-bromoadenosine-3',5'-cAMP or a PKA agonist, N(6)-benzoyl-cAMP, indicating that KOR inhibits cAMP/PKA signaling. Furthermore, KOR-null or dynorphin (an endogenous KOR agonist)-null mice showed a significant increase in overall vascular formation and ectopic vascular invasion into somites at embryonic day -10.5. ECs in these null mice showed significant increase in Flk1 and NRP1, along with reciprocal decrease in plexinD1, which regulates vascular pathfinding. The opioid system is, thus, a new regulator of vascular development that simultaneously modifies 2 distinct vascular properties, EC differentiation and vascular pathfinding.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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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/Dynorphins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, kappa,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
|
| pubmed:issn |
1528-0020
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| pubmed:author |
pubmed-author:FurutaSadayoshiS,
pubmed-author:ImaiSatoshiS,
pubmed-author:KatayamaShioriS,
pubmed-author:KuzumakiNaokoN,
pubmed-author:NagaseHiroshiH,
pubmed-author:NaritaMichikoM,
pubmed-author:NaritaMinoruM,
pubmed-author:SuzukiTsutomuT,
pubmed-author:YamamizuKoheiK,
pubmed-author:YamashitaJun KJK
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| pubmed:issnType |
Electronic
|
| pubmed:day |
21
|
| pubmed:volume |
118
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
775-85
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| pubmed:meshHeading |
pubmed-meshheading:21460241-Animals,
pubmed-meshheading:21460241-Cell Differentiation,
pubmed-meshheading:21460241-Cell Line,
pubmed-meshheading:21460241-Cell Movement,
pubmed-meshheading:21460241-Cyclic AMP,
pubmed-meshheading:21460241-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:21460241-Dynorphins,
pubmed-meshheading:21460241-Embryonic Stem Cells,
pubmed-meshheading:21460241-Endothelial Cells,
pubmed-meshheading:21460241-Female,
pubmed-meshheading:21460241-Gene Expression Regulation, Developmental,
pubmed-meshheading:21460241-Male,
pubmed-meshheading:21460241-Mice,
pubmed-meshheading:21460241-Mice, Inbred C57BL,
pubmed-meshheading:21460241-Mice, Knockout,
pubmed-meshheading:21460241-Neovascularization, Physiologic,
pubmed-meshheading:21460241-Neuropilin-1,
pubmed-meshheading:21460241-Pregnancy,
pubmed-meshheading:21460241-Receptors, Opioid, kappa,
pubmed-meshheading:21460241-Signal Transduction,
pubmed-meshheading:21460241-Vascular Endothelial Growth Factor Receptor-2
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| pubmed:year |
2011
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| pubmed:articleTitle |
The ? opioid system regulates endothelial cell differentiation and pathfinding in vascular development.
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| pubmed:affiliation |
Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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