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Development of novel antibody drugs for inhibition of autoimmune diseases, based on integrin splicing variant functions

Research Project

Project/Area Number 24590072
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionHokkaido University

Principal Investigator

KON Shigeyuki  北海道大学, 薬学研究科(研究院), 准教授 (90344499)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsインテグリン / スプライシングバリアント / 細胞接着 / 酵素阻害剤 / 自己免疫疾患 / 抗体 / インテグリン変異体 / がん転移
Outline of Final Research Achievements

We reported that SFα9, α9 integrin splicing variant, is a functional modulator of wild-type α9 integrin. We identified a inhibitor, which inhibits α9 integrin function, by exploring SFα9-binding molecules. The inhibitor protects mice from various autoimmune diseases.
We identified α4 integrin splicing variant, α4B. Although cells expressing α4B only have little binding to ligands of wild-type, cells co-expressing wild-type α4 integrin and α4B exhibits inhibition of wild-type α4 integrin-dependent cell adhesion. Thus, α4B is a endogenous inhibitory molecule for wild-type α4 integrin.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] Tyk2 is a therapeutic target for psoriasis-like skin inflammation.2014

    • Author(s)
      Ishizaki M, Muromoto R, Akimoto T, Sekine Y, Kon S, Diwan M, Maeda, H, Togi S, Shimoda K, Oritani K, Matsuda T.
    • Journal Title

      Int. Immunol.

      Volume: 26 Issue: 5 Pages: 257-267

    • DOI

      10.1093/intimm/dxt062

    • NAID

      120005522324

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses.2014

    • Author(s)
      Sekine Y, Nishida K, Yamasaki S, Muromoto R, Kon S, Kashiwakura J, Saitoh K, Togi S, Yoshimura A, Oritani K, Matsuda T
    • Journal Title

      J Immunol

      Volume: 192 Issue: 8 Pages: 3488-3495

    • DOI

      10.4049/jimmunol.1300886

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis.2014

    • Author(s)
      Fujita N, Oritani K, Ichii M, Yokota T, Saitoh N, Okuzaki D, Sekine Y, Kon S, Muromoto R, Saitoh K, Yoshimura A, Matsuda T, Kanakura Y.
    • Journal Title

      Eur J Immunol.

      Volume: 44 Issue: 6 Pages: 1791-1801

    • DOI

      10.1002/eji.201344239

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The novel α4B murine α4 integrin splicing variant inhibits α4-dependent cell adhesion.2014

    • Author(s)
      Kouro H, Kon S, Matsumoto N, Miyashita T, Kakuchi A, Ashitomi D, Saito K, Nakatsuru T, Togi S, Muromoto R, Matsuda T.
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 23 Pages: 16389-16398

    • DOI

      10.1074/jbc.m114.553610

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.2014

    • Author(s)
      Kon S, Nakayama Y, Matsumoto N, Ito K, Kanayama M, Kimura C, Kouro H, Ashitomi D, Matsuda T, Uede T.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 12 Pages: e116210-e116210

    • DOI

      10.1371/journal.pone.0116210

    • NAID

      120005540287

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] α9β1 integrin acts as a critical intrinsic regulator of human rheumatoid arthritis.2014

    • Author(s)
      α9β1 integrin acts as a critical intrinsic regulator of human rheumatoid arthritis.
    • Journal Title

      Rheumatology (Oxford).

      Volume: 53 Issue: 3 Pages: 415-424

    • DOI

      10.1093/rheumatology/ket371

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Y14 positively regulates TNF-α-induced NF-κB transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein.2013

    • Author(s)
      Togi S, Shiga K, Muromoto R, Kato M, Souma Y, Sekine Y, Kon S, Oritani K, Matsuda T.
    • Journal Title

      J Immunol

      Volume: 191 Issue: 3 Pages: 1436-1444

    • DOI

      10.4049/jimmunol.1300501

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Jun activation domain-binding protein 1 (JAB1) is required for the optimal response to interferons.2013

    • Author(s)
      Muromoto R, Nakajima M, Hirashima K, Hirao T, Kon S, Shimoda K, Oritani K, Matsuda T.
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 43 Pages: 30969-30979

    • DOI

      10.1074/jbc.m113.485847

    • NAID

      120005397865

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by interacting with caspase-8.2012

    • Author(s)
      Sekine Y, et al
    • Journal Title

      J Immunol

      Volume: 188 Issue: 12 Pages: 6194-6204

    • DOI

      10.4049/jimmunol.1103467

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 新規α9インテグリンリガンドLymphotactinの同定と機能解析2015

    • Author(s)
      中鶴 拓也, 松本 尚樹, 紅露 ひとみ, 松田 正, 今 重之
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] α4インテグリンスプライシングバリアントによるインテグリン機能調節機構の解明と創薬への発展2015

    • Author(s)
      今 重之, 紅露 ひとみ, 中鶴 拓也, 宮下 友惠, 松本 尚樹, 松田 正
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規α4インテグリンバリアントはα4インテグリンの内在性機能阻害因子である2014

    • Author(s)
      紅露ひとみ、松本尚樹、宮下友恵、中鶴拓也、今重之、松田正
    • Organizer
      第51回日本生化学会北海道支部例会
    • Place of Presentation
      札幌
    • Year and Date
      2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規変異型α4インテグリンの同定と機能解析2014

    • Author(s)
      宮下友惠、紅露ひとみ、松本尚樹、今重之、松田正
    • Organizer
      日本薬学会北海道支部第141回例会
    • Place of Presentation
      札幌
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Lymphotactinは新規α9インテグリンリガンドである2014

    • Author(s)
      中鶴拓也、松本尚樹、紅露ひとみ、今重之、松田正
    • Organizer
      日本薬学会北海道支部第141回例会
    • Place of Presentation
      札幌
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 細胞内配列の異なる新規変異型α4インテグリンは α4インテグリン依存性細胞接着を抑制する2013

    • Author(s)
      紅露 ひとみ、今 重之、松田 正
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド、兵庫県
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel secreted alpha4 integrin variant inhibits alpa4 and alpha9 integrin-dependent cell adhesion2013

    • Author(s)
      Shigeyuki Kon and Tadashi Matsuda
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      千葉県幕張メッセ、千葉県
    • Related Report
      2013 Research-status Report
  • [Presentation] Identification of a novel alpha9 integrin ligand, lymphotactin2013

    • Author(s)
      Naoki Matsumoto, Shigeyuki Kon, Tadashi Matsuda
    • Organizer
      第42回日本免疫学会
    • Place of Presentation
      千葉県幕張メッセ、千葉県
    • Related Report
      2013 Research-status Report
  • [Presentation] 細胞内配列の異なる新規変異型α4インテグリンの機能2013

    • Author(s)
      紅露ひとみ、今重之、松田正
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel murine α4 integrin splicing variant is a specific receptor for VCAM-12012

    • Author(s)
      Kon S, Kouro H, Matsuda T
    • Organizer
      The 99th AAI Annual Meeting
    • Place of Presentation
      Hynes Convention Center, Boston, USA
    • Related Report
      2012 Research-status Report
  • [Remarks] がん細胞転移を抑制する新たな細胞接着制御メカニズムを解明

    • URL

      http://www.hokudai.ac.jp/news/140428_pr_pharm.pdf

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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