| Project/Area Number |
08671177
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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 |
内分泌・代謝学
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| Research Institution | Osaka City University |
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Principal Investigator |
NISHIZAWA Yoshiki Medical School, Osaka City University, Associate Professor, 医学部, 助教授 (00128745)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOI Atsushi Medical School, Osaka City University, Lecturer, 医学部, 講師 (90260801)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | vascular calcification / osteopontin / vascular smooth muscle cells / inorganic phosphate / sodium-dependent phosphate co-transporter / 動脈硬化 / ナトリウム依存性リン輸送体 |
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| Research Abstract |
In order to clarify the roles of osteopontin (OPN) in the development of atherosclerotic plaque calcification, we developed an in vitro model of vascular calcification by using bovine vascular smooth muscle cells (BVSMC). Firstly, we examined the effect of human recombinant OPN on BVSMC calcification. Human recombinant OPN dose-dependently increased BVSMC calcification, suggesting that OEN may promote vascular calcification. However, it has been documented that native OPN purified from rat neonatal vascular smooth muscle cells dose-dependently decreased BVSMC calcification. Therefore, phosphorylation of OPN may regulate its action on vascular calcification. Secondly, we investigated the regulation of OPN expression during vascular calcification. We hypothesized that increased concentrations of inorganic phosphate (Pi) resulting from the degradation of beta-glycerophosphate (beta-GP) by alkaline phosphatase (ALP) may modulate the expression of OPN gene in BVSMC.Pi dose-dependently increased BVSMC calcification and the expression of OPN gene. We found that BVSMC is equipped with sodium-dependent phosphate co-transporter. Inhibitors of phosphate transport, phosphonoformic acid and arsenate clearly inhibited BVSMC calcification and induction of OPN gene by Pi. These data suggest that Pi directly regulates vascular calcification through sodium-dependent phosphate co-transporter. Finally, we examined the 1,25- dihydroxyvitamin D3 (l, 25(OH)2D3) on OPN gene expression in BVSMC.l, 25(OH)_2D_3 dose-dependently increased BVSMC calcification and the expression of OPN gene.
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