| Project/Area Number |
22249016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SHIBASAKI Futoshi 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 参事研究員 (90300954)
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| Co-Investigator(Kenkyū-buntansha) |
内藤 暁宏 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (20332372)
内野 博之 東京医科大学, 医学部, 教授 (60266476)
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| Co-Investigator(Renkei-kenkyūsha) |
ONO Tomio 公益財団法人東京都医学総合研究所, 基盤研究センター, 基盤技術研究職員 (60231239)
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| Project Period (FY) |
2010-04-01 – 2013-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000)
Fiscal Year 2012: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2011: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2010: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
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| Keywords | 血管新生 / 核酸医薬 / 虚血性疾患 / 心筋梗塞 / 脳梗塞 / 低酸素 / Int6 / 遺伝子改変マウス / HIF / DFAT / 心筋梗塞モデル / NIBS / ミニブタ / 遺伝子診断・治療 / siRNA創薬 |
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| Research Abstract |
Previously, we found the binding protein Int6/eIF3e fro hypoxia inducible factor 2 alpha (HIF2alpha). The Int6 works as a negative feedback factor to induce degaradation of HIF2alpha even under normoxia. To further investigation of HIF2alpha function, we designated the siRNA and induce it into mouse intradermal space. The injection of siRNA clearly showed the normal angiogenesis of arteries and veins. In addition, we injected the siRNA into ischemic hearts of pigs and rats, ischemic brains of mouse, and injured skin of mice. these experiments demonstrated the clear recovery from ischemic damage and injury. To analyse the mechanisms, we tried to make conditional KO mice to target the Int6 gene. However, we could not the good ES cells after several screening. we now perform recloning of targeting vectors and try again to make the KO mice.
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