| Project/Area Number |
18590889
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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 |
MAESHIMA Yohei Okayama University, University Hospital of Medicine and Dentistry, Senior Assistant Professor (10343287)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Chronic Kidney Disease / Diabetic nephropathy / angmeenesis / peritoneal sclerosis / Peritoneal Dialysis / endostatin / NM-3 / Vasohibin-1 / 糖尿病腎症 / VEGF / アデノウィルスベクター / endostatin peptide / angiopoietin-2 / vasohibin |
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| Research Abstract |
In Japan, the population of Chronic Kidney Disease is estimated as 19. million, facilitating the recognition of CKD as a common disorder. Chronic kidney disease is a risk factor for developing end-stage renal failure and cardiovascular disorders, requiring appropriate preventive management from the early stage. The number of patients requiring dialysis therapies such as hemodialysis or peritoneal dialysis due to end-stage renal failure is increasing, and the main cause of renal failure is diabetic nephropathy. On the other hand, continuous peritoneal dialysis for long-term leads to peritoneal dysfunction, and peritoneal sclerosis. Angiogenesis and vascular dysregulation are considered as potential mechanisms for the development of-peritoneal sclerosis.
We recently reported the therapeutic efficacies of anti-angiogenic tumstatin peptide and endostatin peptide in ameliorating the progression of diabetic nephropathy. Vasohibin is an endothelium-derived negative feedback regulator of angiogenesis, synthesized upon stimulation by VEGF. NM-3 is an orally available compound with the anti-angiogenic as well as anti-tumor effects.
In the present study, we observed the suppressive effects of NM-3 on early diabetic nephropathy in the db/db type 2 diabetse mouse model. NM-3 suppressed high glucose-induced production of VEGF and TGF-beta in mesangial cells, and of VEGF in podocytes.
In chlorhexidine gluconate-induced peritoneal sclerosis mouse model, treatment by endostatin peptide via subcutaneous infusion through osmotic minipumps lead to the inhibition of peritoneal fibrosis.
Treatment with adenoviral vector encoding vasohibin-1 resulted in the amelioration of early diabetic nephropathy in type 1 and 2 diabetes mouse model. Intraperitoneal overexpression of vasohibin-1 lead to the suppression of peritoneal sclerosis.
These results suggested the potential usefulness of anti-angiogenic therapies in patients with chronic kidney disease.
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