| Project/Area Number |
13671098
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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 |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHIZAKA Nobukazu University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20270879)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Ichiro Wakayama Medical University, of Medicine, Associate Professor, 附属病院, 助教授 (10157852)
OHNO Minoru University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00185349)
TSUKAMOTO Kazuhisa University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20251233)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Angiotensin II / Proteinuria / Renal function / Cardiovascular damage / Oxdative stress / Iron metabol ism / Iron overload / Chelator / 腎機能障害 / 高血圧 / 筋障害 / 老化遺伝子 |
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| Research Abstract |
We have reported that continuous administration of angiotensin II caused induction of heme oxygenase-1 (HO-1) in the renal tubular epithelial cells in rats. Recent studies have demonstrated that HO-1 plays a crucial role in maintaining the intracellular iron homeostasis, as well as in heme metabolism. We investigated whether abnormal iron metabolism could be seen in the kidney of rats given chronic angiotensin II. Prussian blue staining showed histologic iron deposition in the tubular epithelial cells where strong HO-1 expression could also be demonstrated after 7-day administration of angiotensin II. Treatment of these rats with iron chelator, deferoxamine, suppressed not only renal iron deposition, but also angiotensin II-induced increase in urinary protein excretion. We generated iron overload rat model to examine iron overload could mimic the effects of angiotensin II on renal function. However, iron overload, achieved by the administration of iron-dextran did not enhance urinary prote in excretion. This was possibly because, unlike angiotensin II-infusion model, iron-dextran treatment caused iron deposition in the mesangial and interstitial cells, but not tubular epithelial cells. Conversely, it is possible, renal tubular iron deposition may play a crucial role in the development of proteinuria.
In other set of experiments, we showed that continuous administration of angiotensin II caused aging-related gene, klotho, in the kidney, suggesting the link between renin-angiotensin system and aging process. We also showed some evidence that abnormal iron metabolism may also involved in one of the mechanisms of angiotensin II-induced cardiovascular damage in our animal model.
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