| Project/Area Number |
12670699
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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 | Nihon University |
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Principal Investigator |
FUKUDA Noboru Nihon University, School of Medicine, Assistant, 医学部, 助手 (40267050)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Yoshiyasu Nihon University, School of Medicine, Assistant, 医学部, 助手 (10267049)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ribozyme / transforming growth factor-β / gene therapy / vascular smooth muscle cell / proliferation / gromerulosclerosis / RNA / キメラ / 増殖 / RT-PCR / ウエスタンブロット |
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| Research Abstract |
We designed hammerhead ribozyme targetting TGF-β_1 mRNA which cleaved the synthetic substrate RNA. We developed DNA-RNA chimeric ribozyme, which significantly inhibited growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). DNA-RNA chimeric ribozyme inhibited TGF-β_1 mRNA and protein in VSMC from SHR. DNA-RNA chimeric ribozyme significantly suppressed expression of TGF-β_1, fibronectin, collagen type I mRNAs in mesangial cells from SHR-SP. In vivo experiments, FITC-labeled ribozyme was efficiently distributed in aorta and kidney. DNA-RNA chimeric ribozyme considerably inhibited hypertrophy of renal capirally artery and gromerulosclerosis in SHR-SP in vivo. We are appling DNA-RNA chimeric ribozyme on coronary stenosis after angioplasty in pig, by which efficiency, dosage, and period of treatment will be determined to develop the DNA-RNA chimeric ribozyme to TGF-β_1 as a gene therapy for arterial proliferative diseases and gromerulosclerosis.
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