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Studies of TACE in bone biology and inflammatory diseases

Research Project

Project/Area Number 19591765
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKeio University

Principal Investigator

HORIUCHI Keisuke  Keio University, 医学部, 講師 (30327564)

Co-Investigator(Kenkyū-buntansha) TOYAMA Yoshiaki  慶應義塾大学, 医学部, 教授 (40129549)
Research Collaborator KIMURA Tokuhiro  慶應義塾大学, 医学部, 助教 (40445200)
OKADA Yasunori  慶應義塾大学, 医学部, 教授 (00115221)
MIYAMOTO Takeshi  慶應義塾大学, 医学部, 准教授 (70383768)
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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords骨・軟骨代謝学 / ADAM17 / TACE / 免疫学 / 骨代謝学 / Ectodomain Shedding / 炎症 / CSF-1
Research Abstract

TNFα converting enzyme (TACE)は膜型前駆蛋白として産生されるTNFαを切断・可溶化する酵素として同定されたが, その後数多くの膜蛋白がその標的分子として同定されている. 本研究では研究代表者が作成したTACE遺伝子改変マスおよびその細胞を利用しTACEがin vivoの病態モデルにおいてもTNFαの可溶化に中心的な役割を担うこと, さらにTACEを広く欠損したマウス作成し, TACEの生体における様々な機能を明らかにした. また生化学的な手法を用いて膜型CSF-1およびFlt3リガンドにTACEが関与していることを解明した.

Report

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

    (20 results)

All 2009 2008 2007 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (8 results)

  • [Journal Article] Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF2009

    • Author(s)
      Horiuchi, K, T. Kimura, T. Miyamoto, K. Miyamoto, H. Akiyama, H. Takaishi, H. Morioka, T. Nakamura, Y. Okada, C. P. Blobel and Y. Toyama.
    • Journal Title

      J Immunol 182

      Pages: 2093-2101

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conditional Inactivation of TACE by a Sox9 Promoter Leadsto Osteoporosis and Increased Granulopoiesis via Dysregulation of IL-17 and G-CSF12009

    • Author(s)
      堀内 圭輔
    • Journal Title

      The Journal of Immunology 182

      Pages: 2093-2101

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ectodomain shedding of FLT3 ligand is mediated by TACE2009

    • Author(s)
      堀内 圭輔
    • Journal Title

      The Journal of Immunology 掲載決定

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling2008

    • Author(s)
      Swendeman, S., K. Mendelson, G. Weskamp, K. Hoiruchi, U. Deutsch, P. Scherle, A. Hooper, S. Rafii, and C. P. Blobel.
    • Journal Title

      Circ Res 103

      Pages: 916-918

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Posttranslational Regulation of Cell Surface Colony Stimulating Factor 12008

    • Author(s)
      Hoiruchi, K., and Y. Toyama
    • Journal Title

      Crit Rev Immunol 28

      Pages: 215-227

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Posttranslational Regulation of Cell-Surface Colony-Stimulating Factor-12008

    • Author(s)
      堀内 圭輔
    • Journal Title

      Critical Reviews in Immunology 28

      Pages: 215-227

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner2007

    • Author(s)
      Horiuchi, K., T. Miyamoto, H. Takaishi, A. Hakozaki, N. Kosaki, Y. Miyauchi, M. Furukawa, J. Takito, H. Kaneko, K. Matsuzaki, H. Morioka, C. P. Blobel, and Y. Toyama.
    • Journal Title

      J Immunol 179

      Pages: 6715-6724

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cutting Edge : TNF-α-Converting Enzyme (TACE/ADAM17) Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock2007

    • Author(s)
      Horiuchi, K., T. Kimura, T. Miyamoto, H. Takaishi, Y. Okada, Y. Toyama, and C. P. Blobel
    • Journal Title

      J Immunol 179

      Pages: 2686-2689

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNFα-Converting Enzyme(TACE/ADAM17)Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock2007

    • Author(s)
      堀内 圭輔
    • Journal Title

      The Journal of Immunology 179

      Pages: 2686-2689

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell surface colony-stimulating factor l can be cleaved by TNFαconverting enzyme or endocytosed in a clathrin-dependent manner2007

    • Author(s)
      堀内 圭輔
    • Journal Title

      The Journal of Immunology 179

      Pages: 6715-6724

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C. P. Blobel and Y. Toyama. 2009. Ectodomain shedding of FLT3 ligand is mediated by TACE

    • Author(s)
      Horiuchi, K, H. Morioka, H. Takaishi, H. Akiyama
    • Journal Title

      J Immunol (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] P. Saftig and C. P. Blobel1. 2009 ADAMs 10 and 17 are differentially regulated components of a general shedding machinery for TGFα, TNFα and other membrane proteins

    • Author(s)
      Le Gall, S. M., P. Bob, K. Reiss, K. Horiuchi, D. Lundell, D. R. Gibb, D. Conrad
    • Journal Title

      Mol Biol Cell 20

      Pages: 1785-1794

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] SOX9プロモーターによりTACEを不活化したマウスではIL-17・G-CSFの発現に異常を呈し、骨粗鬆症、造血異常を生じる2008

    • Author(s)
      堀内圭輔
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-29
    • Related Report
      2008 Final Research Report
  • [Presentation] RANKはADAM17によりSheddingを受け可溶型となる2008

    • Author(s)
      箱崎彰裕
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-29
    • Related Report
      2008 Final Research Report
  • [Presentation] SOX9プロモーターにより TACEを不活化したマウスではIL-17・G-CSFの発現に異常を呈し、骨粗鬆症、造血異常を生じる2008

    • Author(s)
      堀内 圭輔
    • Organizer
      第26回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] RANKはADAM17によりSheddingを受け可溶型となる2008

    • Author(s)
      箱崎 彰裕
    • Organizer
      第26回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] SOX9プロモーターによりTACEの不活化したマウスでは成長障害と骨粗鬆症を生じる2008

    • Author(s)
      堀内圭輔
    • Organizer
      日本整形外科基礎学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-24
    • Related Report
      2008 Final Research Report
  • [Presentation] SOX9プロモーターによりTACEの不活化したマウスでは成長障害と骨粗鬆症を生じる2008

    • Author(s)
      堀内 圭輔
    • Organizer
      第23回日本整形外科基礎学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-10-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] 敗血症性ショックにおけるTACE/ADAM17の機能解析2007

    • Author(s)
      堀内圭輔
    • Organizer
      日本整形外科基礎学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] TACEはin vivoにおいてTNFαの可溶化に必須の分子である2007

    • Author(s)
      堀内圭輔
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2007-07-19
    • Related Report
      2008 Final Research Report 2007 Annual Research Report

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

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