ROLE OF LOX-1, A NOVEL OXIDIZED LOW-DENSITY LIPOPROTEIN RECEPTOR.IN THE PROGRESSION OF RENAL INJURY
| Project/Area Number |
11671028
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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 | UNIVERSITY OF TOKYO |
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Principal Investigator |
NAGASE Miki BRANCH HOSPITAL UNIVERSITY OF TOKYO DEPARTMENT OF INTERNAL MEDICINE RESEARCH ASSOCIATE, 医学部・附属病院・分院, 教務職員 (60302733)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Katsuyuki HEALTH CENTER UNIVERSITY OF TOKYO DEPARTMENT OF INTERNAL MEDICINE LECTURER, 保健センター, 講師 (60184313)
KANAME Shinya BRANCH HOSPITAL UNIVERSITY OF TOKYO DEPARTMENT OF INTERNAL MEDICINE ASSISTANT, 医学部・附属病院・分院, 助手 (60224581)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | KIDNEY / HYPERTENSION / GLOMERULOSCLEROSIS / OXIDIZED LDL RECEPTOR / VASCULAR ENDOTHELIAL CELLS / LOX-1 / 酸化LDL / Dahlラット / SHR / TGF-β |
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| Research Abstract |
Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor abundantly expressed in vascular endothelial cells. We previously reported that LOX-1 expression was markedly enhanced in the vasculatures of hypertensive rats. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-β1 and type I collagen, impaired renal function, and histological glomerulosclerotic changes, all of which were ameliorated by anti-hypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. On the other hand, LOX-1 expression was elevated in the aortas but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was in parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
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Report
(3 results)
Research Products
(6 results)
