| Project/Area Number |
11671106
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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 |
Metabolomics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KAWAKAMI Yasushi Institute of clinical medicine, University of Tsukuba, Associate prfessor, 臨床医学系, 助教授 (70234028)
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| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | VEGF / diabetes / complication / gene expression / 転写調節 / 血管合併症 / 転写抑制物質 / 血管内皮細胞 |
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| Research Abstract |
Vascular endothelial growth factor (VEGF) has the potenUffect to promote angiogenesi, Recently it has been reported that intraocular VEGF levels increase in diabetic retinopathy. Moreover, the inhibition of VEGF by antisense nucleotides or antibody could prevent ocular neovascularization. It is considerable that VEGF is one of the factors worsening diabetic complication. It is suggested that the up-regulation of the VEGF gene is mainly due to hypoxia causing by the obstruction of Small arteries. In this project, the therapy for diabetic complication by the suppression of VEGF gene expression was developed. The luciferase assay was performed with the inseted luciferase gene in the first exon of VEGF gene of the genome DNA(knock-in method). These screening systems could detect a novel material which suppress the gene expression of VEGF gen. The material suppress VEGF and, also increase other 7 genes using DNA array. The administration of the material to the experimental diabetic animal ( GK rat and galactose loading rat) improved the progress of diabetic vascular complication. The retinal vessel proliferation significantly decreased by histology, and the number of apoptotic cell in the retina also decreased. The urinary protein decreased with significant decrease of low-molecular weight protein excretion.
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