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Analysis and clinical application of normal blood vessel inducement by Int6-siRNA

Research Project

Project/Area Number 19590327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

CHEN Li  Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (30425681)

Co-Investigator(Kenkyū-buntansha) SHIBASAKI Futoshi  財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 副参事研究員 (90300954)
TOI Masakazu  財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (10207516)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords血管新生 / siRNA / 低酸素反応因子 / 癌抑制因子 / 虚血 / 動物モデル / 低酸素反応性因子 / RNA干渉 / 遺伝子導入 / 転写因子 / 翻訳因子
Research Abstract

酵母のTwo Hybrid 系を用いて、低酸素反応因子HIF2alpha/EPAS1に関して新規結合因子Int6/eIF3eを同定し、解析の中で、Int6はHIF2alphaに特異的に結合し、HIF1alphaとは異なった蛋白分解機序であることを判明した。また、Int6に特異的なsiRNAはHIF2alphaの発現を安定化した為、各種増殖因子、血管新生因子の分泌されたことから、Int6siRNAをマウスの皮下に発現させたところに、非常に顕著な正常な動脈、静脈を誘導されたことが認められた。このことから、Int6はHIF2alphaを介した血管新生のマスタースイッチの一つであることが明らかになった。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (28 results)

All 2009 2008 2007 Other

All Journal Article (7 results) (of which Peer Reviewed: 1 results) Presentation (19 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Int6 as a novel regulator of normal vessel formation through hypoxia inducible factor 2 alpha.2009

    • Author(s)
      Futoshi Shibasaki, Li Chen, Kazuyo Uchida, Alexander Endler
    • Journal Title

      Exp.Mol.Med. in press

      Pages: 0-0

    • Related Report
      2008 Final Research Report
  • [Journal Article] 最新イムノPCR法:MUSTag法を用いた極微量タンパク質の同時多項目測定2008

    • Author(s)
      森實芳仁、石川雄一郎、Li Chen、内田和代、芝崎太
    • Journal Title

      実験医学 26(11)

      Pages: 802-810

    • Related Report
      2008 Final Research Report
  • [Journal Article] 超高感度多項目解析(MUSTag)法による臨床診断への応用2008

    • Author(s)
      芝崎太、森實芳仁、石川雄一郎, 槇坂典子、小俣結子、陳リー、内田和代
    • Journal Title

      臨床病理 56(9)

      Pages: 1759-1765

    • NAID

      10024960491

    • Related Report
      2008 Final Research Report
  • [Journal Article] Probing the molecular mechanisms of neuronal degeneration : importance of mitochondrial dysfunction and calcineurin activation2008

    • Author(s)
      Uchino H. Kuroda Y, Morota S. Hirabayashi G. Ishii N. Shibasaki F, Ikeda Y, Hansson MJ, Elmer E
    • Journal Title

      J Anesth 22

      Pages: 253-62

    • NAID

      10021942407

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian tumor suppressor Int6 specifically targets HIF-2alpha to degradation by hypoxia- and pVHL- independent regulation.2007

    • Author(s)
      Chen L, Uchida K, Endler A, Shibasaki F.
    • Journal Title

      J Biol Chem. 282(17)

      Pages: 12707-16

    • Related Report
      2008 Final Research Report
  • [Journal Article] Mammalian tumor suppressor Int6 specifically targets HIF-2alpha to degradation by hypoxia-and pVHL-independent regulation.2007

    • Author(s)
      Chen L., Uchida K., Endler A., Shibasaki F.
    • Journal Title

      J Biol Chem. 282(17)

      Pages: 12707-12716

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Int6 as a novel regulator of normal vessel formation through hypoxia inducible factor 2 alpha. (Review Article)

    • Author(s)
      Futoshi Shibasaki, Li Chen, Kazuyo Uchida, Alexander Endler
    • Journal Title

      Exp. Mol. Med (in press)

    • Related Report
      2008 Annual Research Report
  • [Presentation] Novel Function of Int6/HIF2α Pathway in Physiological Angiogenesis2008

    • Author(s)
      F., Shibasaki, L., Chen, K., Uchida, A., Endler, S., Horiguchi, Y., Suzuki, M., Toi
    • Organizer
      KSMBMB
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 免疫抑制から神経保護作用へ:シクロスポリンの分子クロストーク.「明らかになるシクロスポリンの新たな Profile」2008

    • Author(s)
      芝崎太
    • Organizer
      第49回日本神経学会総会ランチョンセミナー
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-05-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] siRNA-Int6による低酸素反応性(HIF2α)の活性調節と正常血管との関係2008

    • Author(s)
      Li Chen、内田和代、Alexander Endler, 芝崎 太
    • Organizer
      第81回日本生化学会大会 第31回日本生化学学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2008 Final Research Report
  • [Presentation] eIF3e/int6 Specifically Degradate HIF-2a By Hypoxia- And pVHL-Independent Regulation2008

    • Author(s)
      Li Chen, Masakazu Toi, Futoshi Shibasaki1
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      Nagoya Congress center
    • Related Report
      2008 Final Research Report
  • [Presentation] Int6のノックダウンによる低酸素反応性因子(HIF2α)の活性調節と正常血管創生2008

    • Author(s)
      陳リー、内田和代、Alexander Endler, 芝崎太
    • Organizer
      第6回Cell Biology Summer Meeting
    • Place of Presentation
      千葉・鴨川
    • Related Report
      2008 Final Research Report
  • [Presentation] Int6のノックダウンによる低酸素反応性因子(HIF2α)の活性調節と正常血管創生2008

    • Author(s)
      陳リー, 内田和代, Alexander Endler, 芝崎太
    • Organizer
      第6回 Cell Biology Summer Meeting 2008
    • Place of Presentation
      千葉・鴨川
    • Related Report
      2008 Annual Research Report
  • [Presentation] siRNA-Int6 triggers normal angiogenesis directly by hypoxia-independent stabilization of HIF2alpha2008

    • Author(s)
      F., Shibasaki, L., Chen, Toi
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Int6によるHIF2αの低酸素非依存的な正常血管新生制御と Int6-siRNA を用いた創薬2008

    • Author(s)
      芝崎太, 陳リー, 内田和代, Alexander Endler
    • Organizer
      BMB2008
    • Place of Presentation
      兵庫・神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] siR:NA-Int6による低酸素反応性因子(HIF2α)の活性調節と正常血管創生との関係2008

    • Author(s)
      陳リー, 内田和代, Alexander Endler, 芝崎太
    • Organizer
      BMB2008
    • Place of Presentation
      兵庫・神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規結合因子Int6/eIF3eによるHIF2aの低酸素非依存的な制御2007

    • Author(s)
      陳リー 内田和代、Alexander Endler、飯島修、芝崎太
    • Organizer
      第30回日本分子生物会年会・第80回日本生化学学会大会合同大会
    • Place of Presentation
      神奈川・横浜
    • Year and Date
      2007-12-14
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素因子HIF2aに関わるInt6のNegative Feedback 制御2007

    • Author(s)
      陳リー 内田和代、飯島修、森實芳仁、芝崎太
    • Organizer
      第5回がんとハイポキシア研究会
    • Year and Date
      2007-12-01
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素因子HIF2aに関わるInt6のNegative Feedback制御2007

    • Author(s)
      陳 リー, 内田 和代, Alexander Endler, 飯島 修, 森實 芳仁, 芝崎 太
    • Organizer
      第5回がんとハイポキシア研究会
    • Place of Presentation
      がんセンター東病院内講堂
    • Year and Date
      2007-12-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] HIF2αの新規抑制因子Int6による制御機構とint6-siRNAを用いた正常血管新生2007

    • Author(s)
      陳 リー, 芝崎 太
    • Organizer
      がん、分子標的治療研究会
    • Place of Presentation
      大阪国際交流センター
    • Year and Date
      2007-07-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] Int6 Triggers Normal Angiogenesis in Mouse Skin Directly by Hypoxia-Independent Stabilisation of HIF-2a2007

    • Author(s)
      Li Chen, Kazuyo Uchida, Alexander Endler, Shin-ichiro Horiguchi, Yosuke Suzuki and Futoshi Shibasaki
    • Organizer
      第66回日本癌学会学術総会
    • Related Report
      2008 Final Research Report
  • [Presentation] Int6 Specifically Targets HIF-2a to Degradation By Hypoxia- And pVHL-Independent Regulation.2007

    • Author(s)
      陳リー 内田和代、Alexander Endler、飯島修、芝崎太
    • Organizer
      第6回Cell Biology Summer Meeting 2007
    • Related Report
      2008 Final Research Report
  • [Presentation] Int6; New Target for Angiogensis(1) eIF3e/int6 Specifically Targets HIF-2a for Degradation By Hypoxia- And pVHL-Independent Regulation.2007

    • Author(s)
      Li Chen, Kazuyo Uchida, Alexander Endler, Osamu Iijima and Futoshi Shibasaki
    • Organizer
      4th Annual Symposium of the American Heart Association Council on Basic Cardiovascular Science
    • Place of Presentation
      the Keystone Conference Center, Keystone, Colorado, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Int6 for Angiogenesis(1) eIF3e/int6 Specifically Targets HIF-2a For Degradation By Hypoxia-And pVHL-Independent Regulation2007

    • Author(s)
      Li Chen, Kazuyo Uchida, Alexander Endler, Osamu Iijima and Futoshi Shibasaki
    • Organizer
      第4回Annual Symposium the American Heart Association
    • Place of Presentation
      keystone(アメリカ)
    • Related Report
      2007 Annual Research Report
  • [Presentation] 低酸素因子HIF-2□の新規抑制因子eIF3e/int6による制御機序の解明2007

    • Author(s)
      陳 リー, 内田 和代, Alexander Endler, 飯島 修, 芝崎 太
    • Organizer
      セルバイオロジーサマーミーティング
    • Place of Presentation
      伊東
    • Related Report
      2007 Annual Research Report
  • [Presentation] 新規結合因子eIF3e/int6によるHIF2aの低酸素非依存的な制御機序2007

    • Author(s)
      陳 リー, 内田 和代, Alexander Endler, 飯島 修, 芝崎 太
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rinshoken.or.jp/MCP/Index/ganseikatu_index.htm

    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞死を予防するための医薬剤2009

    • Inventor(s)
      芝崎 太、陳 リー
    • Industrial Property Rights Holder
      財団法人東京都医学研究機構
    • Industrial Property Number
      2009-070529
    • Filing Date
      2009-03-23
    • Related Report
      2008 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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