| Project/Area Number |
12470209
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
FUJITA Toshiro Faculty of Medicine, Department of Nephrology and Endocrinology, Professor, 医学部附属病院, 教授 (10114125)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOSAWA Tatsuo Faculty of Medicine, Department of Nephrology and Endocrinology, Research Associate, 医学部附属病院, 助手 (90231365)
TAKAHASHI Katsutoshi Faculty of Medicine, Department of Nephrology and Endocrinology, Research Associate, 医学部附属病院, 助手 (00292863)
KANAME Shinya Faculty of Medicine, Department of Nephrology and Endocrinology, Research Assciate, 医学部附属病院, 助手 (60224581)
長瀬 美樹 東京大学, 医学部・附属病院, 客員研究員 (60302733)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | LOX-1 / Renal Damage / Angiotensin II / Atherosclerosis / Hypertension / Oxidative Stress / TGFβ / Renal Intestitial / oxidized LDL / Dahl Rat / PRARγ / Redox / Diahetes / flk-1 / tie2 / Hypertension / Kidney / Nephrosclerosis / Salt / mineralocorticoid / transgenic rat |
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| Research Abstract |
Lectin-like oxidized LDL receptor (LOX-1), which has been firstly demonstrated to be oxidized LDL receptor in vascular endothelial cells, has reported to be enhanced in vasculature of model animals of common diseases that cause atherosclerosis. In fact, LOX-1 increases the expression of several factors relevant to atherosclerosis. Thus, LOX-1 has been considered to play an important role of the pathophysiology of atherosclerosis. We focused the role of LOX-1 in the development of renal damage. We demonstrated that renal LOX-1 expression was increased in salt-loaded Dahl salt-sensitive rats, which are well-known hypertensive renal damage model. In contrast, renal LOX-1 was not enhanced in spontaneously hypertensive rats, in which blood pressure was similarly elevated without renal dysfunction. Moreover, renal LOX-1 expression was stimulated in the other renal damage models such as 5/6-nephrectomized rats and unilateral urethral obstruction mice. Subacute TNFα stimulation also enhance renal LOX-1 expression. Therefore, LOX-1 may be important in the development of any kinds of renal damage. Also, agents to inhibit the renin-angiotensin system and antioxidants ameliorated renal damage associated with reduction of LOX-1 expression. Thus, angiotensin II and oxidative stress may attribute to the development of renal damage through increase in LOX-1 expression.
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