| 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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| 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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