2001 Fiscal Year Final Research Report Summary
Development of therapy for the diabetic vascular complication by supression of VEGF gene expression
| 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
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| Keywords | VEGF / diabetes / complication / gene expression |
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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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[Publications] Sone H, Sakauchi M, Takahashi A, Suzuki H, Inoue N, lida K, Shimano H, Toyoshima H, Kawakami Y, Okuda Y, Matsuo K, Yamada N: "Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity"Life Sci.. 69(16). 1861-9 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Nakajima T, Iwasawa K, Oonuma H, Imuta H, Hazama H, Asano M, Morita T, Nakamura F, Suzuki J, Suzuki S, Kawakami Y, Omata M, Okuda Y: "Troglitazone inhibits voltage-dependent calcium currents in guinea pig cardiac myocytes."Circulation. 99(22). 2942-50 (1999)
Description
「研究成果報告書概要(欧文)」より
