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rdf:type |
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lifeskim:mentions |
umls-concept:C0010592,
umls-concept:C0029418,
umls-concept:C0030685,
umls-concept:C0078058,
umls-concept:C0085149,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1256770,
umls-concept:C1283071,
umls-concept:C1963578,
umls-concept:C2349975
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-16
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pubmed:abstractText |
We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In addition, p70 S6 kinase activated by FGF-2 negatively regulates VEGF release via SAPK/JNK. In the present study, we investigated the effects of tacrolimus (FK506) and cyclosporine A, well-known immunosuppressants, on the FGF-2-induced VEGF release in these cells. Tacrolimus, but not cyclosporine A which alone had no effect on VEGF basal levels, significantly enhanced FGF-2-stimulated VEGF release. Tacrolimus markedly enhanced FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP or p38 MAP kinases. SP600125, a specific inhibitor of SAPK/JNK, reduced the amplification by tacrolimus of the FGF-2-induced VEGF release. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by tacrolimus. These results strongly suggest that tacrolimus enhances FGF-2-stimulated VEGF release via up-regulation of SAPK/JNK through modulating p70 S6 kinase in osteoblasts.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1107-3756
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pubmed:author |
pubmed-author:AdachiSeijiS,
pubmed-author:HaradaAtsushiA,
pubmed-author:KozawaOsamuO,
pubmed-author:Matsushima-NishiwakiRieR,
pubmed-author:MinamitaniChihoC,
pubmed-author:MizutaniJunJ,
pubmed-author:NatsumeHideoH,
pubmed-author:OtsukaTakanobuT,
pubmed-author:TakaiShinjiS,
pubmed-author:TakedaJunJ,
pubmed-author:TokudaHaruhikoH,
pubmed-author:YamauchiJunichiJ
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
267-72
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19148552-Animals,
pubmed-meshheading:19148552-Cells, Cultured,
pubmed-meshheading:19148552-Cyclosporine,
pubmed-meshheading:19148552-Enzyme Inhibitors,
pubmed-meshheading:19148552-Fibroblast Growth Factor 2,
pubmed-meshheading:19148552-Immunosuppressive Agents,
pubmed-meshheading:19148552-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:19148552-Mice,
pubmed-meshheading:19148552-Osteoblasts,
pubmed-meshheading:19148552-Ribosomal Protein S6 Kinases, 70-kDa,
pubmed-meshheading:19148552-Tacrolimus,
pubmed-meshheading:19148552-Up-Regulation,
pubmed-meshheading:19148552-Vascular Endothelial Growth Factor A
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pubmed:year |
2009
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pubmed:articleTitle |
Tacrolimus but not cyclosporine A enhances FGF-2-induced VEGF release in osteoblasts.
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pubmed:affiliation |
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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