| Project/Area Number |
60570291
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
ORITA Yoshimasa First department of Medicine, Assistant professor, 医学部, 講師 (70028398)
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| Co-Investigator(Kenkyū-buntansha) |
田中 善 大阪大学, 医学部附属病院, 医員
FUJIWARA Yoshihiro First department of Medicine, Assistant professor, 医学部, 助手 (60135473)
TANAKA Yoshimu First department of Medicine, Senior clinical fellow
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Cultured rat mesangial cells / Angiotensin <II> / Phosphoinositide metabolism / Cキナーゼ / イノシトールリン脂質代謝 |
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| Research Abstract |
Mesangial cell proliferation is a common feature in various forms of glomerulonephritis. To clarify the mechanism of mesangial cell proliferation, we studied the effect of angiotensin <II> upon DNA synthesis and phosphoinositide metabolism in cultured rat mesangial cell (CRMC). CRMCs were prepared by the culture of rat isolated glomeruli.
1. DNA synthesis : The DNA synthesis was evaluated by measuring the incorporation of [ <^3H> ]-thymidine into CRMCs. With insulin(5 <micro> g/ml) or 10%-plasma derived serum, angiotensin <II> ( <10^(-5)> , <10^(-7)> M) significantly stimulated DNA synthesis in first subcultured CRMCs at the quiescent state. Saralasin ( <10^(-5)> M), an angiotensin <II> antagonist, blocked the increase of DNA synthesis by angiotensin <II> ( <10^(-7)> M) and insulin. The dependence on insulin of the growth effect of angiotensin <II> was similar to that of platelet-derived growth factor in CRMCs.
2. Phosphoinositide metabolism : The effect of angiotensin <II> on phosphoinositide metabolism was studied in CRMCs prelabeled with [ <^3H> ]-arachidonic acid. Angiotensin <II> (10 <^(-6)M> ) decreased [ <^3H> ]-phosphatidylinositol-4, 5-bisphosphate ( <PIP_2> ) with a concomitant increase in [ <^3H> ]-diacylglycerol within 15 sec. The decreasing effect of angiotensin <II> upon [ <^3H> ]- <PIP_2> was dose dependent and inhibited by saralasin, but was not affected by use of <Ca^(2+)> free medium containing 0.5mM EGTA. These results suggest that after binding to mesangial receptors, angiotensin <II> induces rapid <PIP_2> hydrolysis by phospholipase C independently of extracellular <Ca^(2+)> .
In conclusion, angiotensin <II> exerts growth effect upon CRMCs probably through enhancing phosphoinositide metabolism.
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