| Project/Area Number |
18592060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YOKOYAMA Chieko Tokyo Medical and Dental University, Graduate SchoolDepartment of Cellular Physiological Chemistry, COE program Research Professor (90200914)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Ikuo Tokyo Medical and Dental University, Graduate School Department of Cellular Physiological Chemistry, Professor (60100129)
NAKAHAMA Kenichi Tokyo Medical and Dental University, Graduate School Department of Cellular Physiological Chemistry, Associate Professor (60281515)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | prostaglandih / prostacyclin / kidney / inflammation / vascular disorders / bone |
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| Research Abstract |
Prostacyclin (PGI_2) is the powerful physiological lipid mediator which has the platelet anti-aggregating and vasorelaxant effects, and regulation of the cell growth. Arachidonic acid is converted to PGH_2 by cyclooxygenase and PGI_2 is converted from the PGH_2 by the catalytic reaction of PGI_2 synthase (PGIS). PGI_2 acts through the PGI_2 receptor on the cell membranes and also acts as the endogenous ligand of PPARδ which is the nuclear receptor. Recently, relationship of inflammation and PGI2-PPARδ signaling has gotten attention. However, the detail mechanism is not clear. In this study, we have tried to clarify the effects of PGI_2 on inflammation and the reaction mechanisms. The obtained results are as follows.
1. Administration of PGI_2 receptor agonist, Beraprost sodium was not prevented development of kidney disorders of PGI_2-deficient mice (PGIS-KO mice). The blood urinary nitrogen (BUN) levels of the PGIS-Kotg mice, which were generated by breeding PGIS-KO mice and PGIS transgenic mice, significantly decreased compared with those of PGIS-KO mice. The result suggests that endogenous PGI_2 may regulate the progression of kidney diseases of PGI2-deficient mice and may have some anti-inflammatory effect.
2. Little is known about the relation between PGI_2 and the bone metabolism. To study on the relationship we have observed influence of the PGI_2 deficiency in bone formation. As a result, we have recognized the increase of trabecular bone density and the decrease of total bone density in the fibulae of female PGI_2-deficient mice. The results suggest that PGI2 may participate in the maintenance of the quantity of the normal bone and of microstructure of the bone.
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