| Project/Area Number |
13470337
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Nagasaki University Graduate School of Medical Science |
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Principal Investigator |
KANDA Shigeru Nagasaki University Graduate School of Medical Science, Department of Molecular Microbiology and Immunology, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20244048)
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| Co-Investigator(Kenkyū-buntansha) |
NOMATA Koichiro Nagasaki University Hospital, Department of Urology, Lecturer, 医学部附属病院, 講師 (80189430)
KANETAKE Hiroshi Nagasaki University Graduate School of Medical Science, Department of Urology, Professor, 大学院・医歯薬学総合研究科, 教授 (50100839)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | angiogenesis / endothelial cells / c-Fes / c-Fyn / FGF-2 / tube formation / stromal cell-derived factor-1 / sonic hedgehog / FGF / Tie2 / シグナル伝達 |
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| Research Abstract |
We investigated the signal transduction pathways leading to cellular responses of endothelial cells for establishment of endothelial cell-specific antiangiogenic therapy. C-Fes is a protein tyrosine kinase, which is exclusively expressed in endothelial cells as well as hematopoietic cells. We identified that angiopoietin 2 (Ang2) induced migration and tube formation by nurine brain capillary endothelial cells, denoted IBE cells. Ang2-induced migration was dependent on phosphoinositide 3-kinase (PI3-kinase) and activation of PI3-kinase required c-Fes activity. In cells treated with stromal cell-derived factor-1 (SDF-1) and sonic hedgehog (Shh) also induced tube formation of endothelial cells in PI3-kinase- and c-Fes-dependent manner. These results indicate that c-Fes and is important for ligand-dependent activation of PI3-kinase and subsequent cellular responses of endothelial cells. Tube formation was regulated by c-Fyn, a member of Src family protein tyrosine kinase, in FGF-2- and Ang2-treated cells, suggesting that c-Fyn plays pivotal role in tube formation of endothelial cells. To examine the details of downstream signaling pathways of c-Fes and c-Fyn would thus be great importance to find new targets for antiangiogenic therapies, which are specific for endothelial cells.
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