Role of endothelial cell selective adhesion molecule (ESAM) in the genesis of diabetic vasculopathy
| Project/Area Number |
17590734
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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 |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
ISHIDA Tatsuro Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (00379413)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Mitsuhiro Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40135794)
HIRATA Ken-ichi Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20283880)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | adhesion molecule / diabetes mellitus / endothelium / retinopathy / angiogenesis / atherosclerosis / diabetic vasculopathy / inlammation |
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| Research Abstract |
1) Role of ESAM in diabetes mellitus
Endothelial cell selective adhesion molecule (ESAM) is a new member of the immunoglobulin family adhesion molecule which has been cloned from vascular endothelial cells. ESAM expression is selectively restricted to vascular endothelial cells. To clarify the role of ESAM in the genesis of diabetic vasculopathy, aortic endothelial cells were isolated from wild-type and ESAM knockout mice and endothelial permeability was evaluated using the modified Boyden chamber system with the Evance Blue dye. The ESAM deficient endothelial cells showed a significant increase of endothelial cell permeability when compared to wild type endothelial cells. Consistent with this result, ESAM knockout mice showed marked albuminuria when compared to wild type mice. When wild type and ESAM knockout mice were injected with streptozotocin to evoke diabetes, ESAM knockout mice showed severer albuminuria and hypoalbuminemia. These results indicate that ESAM regulates endothelial permeability, and a decrease in ESAM expression increase the albuminuria. Thus, ESAM may play an important role in the pathophysiology of early stages of diabetic nephropathy by modulating glomerular permeability.
2) Role of ESAM in atherosclerosis
ESAM knockout mice were bred with apoE knockout mice to generate the ESAM-apoE double knockout mice. Aortic atherosclerotic lesions were evaluated by Sudan III staining. Atherosclerotic lesion of ESAM-apoE double knockout mice were significantly smaller than the control apoE knockout mice. The macrophage content in the atherosclerotic lesion was smaller in ESAM-apoE double knockout mice than in apoE knockout mice. These results indicate that ESAM regulates the formation of atherosclerosis by modulating eodnthelial-hepatopoietic cell interaction.
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Report
(3 results)
Research Products
(27 results)
