| Project/Area Number |
14370794
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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 |
Laboratory medicine
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| Research Institution | The University of Tokyo (2003)
山梨医科大学 (2002) |
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Principal Investigator |
YATOMI Yutaka The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (60200523)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Yukio The University of Tokyo, Faculty of Medicine, Professor, 医学部, 教授 (30134539)
TAKAHUTA Toshiroh The University of Tokyo, Faculty of Medicine, Research Associate, 医学部, 助手 (70334860)
ASAZUMA Naoki The University of Tokyo, Faculty of Medicine, Research Associate, 医学部, 助手 (60293445)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | sphingosine 1-phosphate / vascular biology / endothelial cells / smooth muscle cells / laboratory medicine / EDG / Rho / スフインゴシン1-リン酸 |
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| Research Abstract |
We have examined the significance of sphingosine 1-phosphate (Sph-1-P) in vascular biology, and tried its application into laboratory medicine. Followings are the main results obtained.
1)EDG receptors in vascular endothelial cells and smooth muscle cells
Human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs) were found to express EDG-5 protein weakly and abundantly, respectively. An EDG-5 antagonist reversed the. inhibitory effect of Sph-1-P on SMC migration, and further enhanced Sph-1-P-stunulatecl HUVEC migration. Accordingly, it was indicated that specific regulation of Sph-1-P-modulated migration responses in vascular cells can be achieved by EDG-55 antagonists and that manipulation of Sph-1-P biological activities by the EDG antagonist may lead to a therapeutical application to control vascular diseases. Furthermore, SphlP was found to induce the contraction of coronary artery SMCs through the EDG-5/Rho signaling.
2) EDG receptors in hepatocytes
Sph-1-P was found to exert an anti-proliferative effect on rat hepatocytes, which is an exceptional phenomenon considering an established concept that Sph1-P is a mitogen in many cell types.
3) Sph-1-P assay
We have.established the Sph-1-P assay system by SphlP coupling with o'phthalaldehyde, followed by separation with HPLC and fluorescence monitoring. Now we are trying to determine the best plasma sampling conditions for its application to laboratory medicine.
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