| Project/Area Number |
13671116
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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 | OKAYAMA UNIVERSITY |
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Principal Investigator |
SHIKATA Kenichi Okayama University, Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (00243452)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Jun Okayama University, Graduate School of Medicine and Dentistry, Assistant Professor, 大学院・医歯学総合研究科, 助手 (30294408)
MAKINO Hirofumi Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (50165685)
松田 充浩 岡山大学, 医学部・附属病院, 助手 (20314669)
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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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Diabetic nephropathy / Macrophage / Kidney / Inflammation / ICAM-1 / Glomerulus / Interstitium / TGF-β / ICAM-1 / サイトカイン / DNAアレイ / 糖尿病 / 腎臓 / コラーゲン / DNA |
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| Research Abstract |
Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of macrophage in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. Moreover, we investigated the gene expression profiles in the kidneys. of these mice using DNA microarray system. Proinflammatory genes are up-regulated in the kidneys of diabetic ICAM-1(+/+) mice, while the expression levels of these genes were decresased in diabetic ICAM-1(-/-) mice as compared to ICAM-1(+/+) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.
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