• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Inhibition of an endothelial cell surface molecule by its internalization.

Research Project

Project/Area Number 20590399
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

NARAZAKI Masashi  Osaka University, 大学院・医学研究科, 助教 (00467573)

Co-Investigator(Kenkyū-buntansha) TANAKA Toshio  大阪大学, 大学院・医学系研究科, 准教授 (40273651)
OGATA Atsushi  大阪大学, 大学院・医学系研究科, 助教 (90309451)
Research Collaborator TOSATO Giovanna  NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL CANCER INSTITUTE, PRINCIPAL INVESTIGATOR
SEGARRA Marta  NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL CANCER INSTITUTE, FELLOW
HOU Xu  NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL EYE INSTITUTE, FELLOW
LI Xuri  NATIONAL INSTITUTE OF HEALTH, USA, NATIONAL EYE INSTITUTE, PRINCIPAL INVESTIGATOR
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords血管新生 / 受容体 / 発現制御 / 血管内皮細胞 / Neuropilin / 内在化 / 薬理学 / くり込み薬 / 癌
Research Abstract

Neuropilin-1 (NRP1) is the cell surface receptor shared by Sema3A and VEGF_<165>. We showed that certain scavenger receptor ligands, sulfated polysaccharides including dextran sulfate, fucoidan, poly(G) and oligo G, induced internalization of endothelial cell-surface of NRP1 and blocked the binding and in vitro function of Sema3A and VEGF_<165>. Polysaccharides, poly or oligo (A), (T), (C) did not share this property. Administration of fucoidan or oligo G to mice reduced VEGF_<165>-induced angiogenesis in vivo. These results identify certain sulfated polysaccharides and oligo G as inducers of internalization and functional inhibition of NRPI, and provide poof-of-principle that engineered receptor internalization is an effective strategy for reducing levels and function of cell-surface receptors.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2010 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (3 results) Remarks (4 results)

  • [Journal Article] Oligo-guanosine nucleotide induces neuropilin-1 internalization in endothelial cells and inhibits angiogenesis.2010

    • Author(s)
      Narazaki M, Segarra M, Hou X, Tanaka T, Li X, Tosato G.
    • Journal Title

      Blood 116(16)

      Pages: 3099-107

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tocilizumab for the treatment of rheumatoid arthritis.2010

    • Author(s)
      Tanaka T, Ogata A, Narazaki M.
    • Journal Title

      Expert Rev Clin Immunol.

      Volume: 6(6) Pages: 843-54

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab.2010

    • Author(s)
      Shima Y, Kuwahara Y, Murota H, Kitaba S, Kawai M, Hirano T, Arimitsu J, Narazaki M, Hagihara K, Ogata A, Katayama I, Kawase I, Kishimoto T, Tanaka T.
    • Journal Title

      Rheumatology (Oxford).

      Volume: 49(12) Pages: 2408-12

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligo-guanosine nucleotide induces neuropilin-1 internalization in endothelial cells and inhibits angiogenesis.2010

    • Author(s)
      Narazaki M, Segarra M, Hou X, Tanaka T, Li X, Tosato G.
    • Journal Title

      Blood.

      Volume: 116(16) Pages: 3099-107

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of a patient with remitting seronegative, symmetrical synovitis with pitting oedema with a humanized anti-interleukin-6 receptor antibody, tocilizumab.2010

    • Author(s)
      Tanaka T, Hagihara K, Shima Y, Narazaki M, Ogata A, Kawase I, Kishimoto T.
    • Journal Title

      Rheumatology(Oxford).

      Volume: 49(4) Pages: 824-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Minimal influence of tocilizumab on IFN-gamma synthesis by tuberculosis antigens.2010

    • Author(s)
      Ogata A, Mori M, Hashimoto S, Yano Y, Fujikawa T, Kawai M, Kuwahara Y, Hirano T, Arimitsu J, Hagihara K, Shima Y, Narazaki M, Yokota S, Kishimoto T, Kawase I, Tanaka T.
    • Journal Title

      Mod Rheumatol.

      Volume: 20(2) Pages: 130-3

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis : a randomized double-blind placebo-controlled trial2009

    • Author(s)
      Kawai M, Hirano T, Arimitsu J, Higa S, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, Ogata A, Koyanagi M, Kai T, Shimizu R, Moriwaki M, Suzuki Y, Ogino S, Kawase I, Tanaka T.
    • Journal Title

      Int Arch Allergy Immunol. 149(4)

      Pages: 359-368

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventative effect of a flavonoid, enzymatically modified isoquercitrin on ocular symptoms of Japanese cedar pollinosis2009

    • Author(s)
      Hirano T, Kawai M, Arimitsu J, Ogawa M, Kuwahara Y, Hagihara K, Shima Y, Narazaki M, Ogata A, Koyanagi M, Kai T, Shimizu R, Moriwaki M, Suzuki Y, Ogino S, Kawase I, Tanaka T.
    • Journal Title

      Allergol Int. 58(3)

      Pages: 373-382

    • NAID

      10025867444

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid improvement of AA amyloidosis with humanised anti-interleukin 6 receptor antibody treatment.2009

    • Author(s)
      Nishida S, Hagihara K, Shima Y, Kawai M, Kuwahara Y, Arimitsu J, Hirano T, Narazaki M, Ogata A, Yoshizaki K, Kawase I, Kishimoto T, Tanaka T.
    • Journal Title

      Ann Rheum Dis. 68(7)

      Pages: 1235-1236

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imatinib mesylate inhibited rat adjuvant arthritis and PDGF-dependent growth of synovial fibroblast via interference with the Akt signaling pathway.2009

    • Author(s)
      Terabe F, Kitano M, Kawai M, Kuwahara Y, Hirano T, Arimitsu J, Hagihara K, Shima Y, Narazaki M, Tanaka T, Kawase I, Sano H, Ogata A.
    • Journal Title

      Mod Rheumatol. 19(5)

      Pages: 522-529

    • NAID

      10025866744

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of reactive arthritis with a humanized anti-interleukin-6 receptor antibody, tocilizumab.2009

    • Author(s)
      Tanaka T, Kuwahara Y, Shima Y, Hirano T, Kawai M, Ogawa M, Arimitsu J, Hagihara K, Narazaki M, Ogata A, Kawase I, Kishimoto T.
    • Journal Title

      Arthritis Rheum. 61(12)

      Pages: 1762-1764

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sustained response to tocilizumab, anti-interleukin-6 receptorantibody, in two patients with refractory relapsing polychondritis.2009

    • Author(s)
      Kawai M, Hagihara K, Hirano T, Shima Y, Kuwahara Y, Arimitsu J, Narazaki M, Ogata A, Kawase I, Kishimoto T, Tanaka T.
    • Journal Title

      Rheumatology(Oxford) 48(3)

      Pages: 318-319

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Etanercept improved primary biliary cirrhosis associated withrheumatoid arthritis.2009

    • Author(s)
      Ogata A, Terabe F, Nakanishi K, Kawai M, Kuwahara Y, Hirano T, Arimitsu J, Hagihara K, Shima Y, Narazaki M, Tanaka T, Kawase I.
    • Journal Title

      Joint Bone Spine 76(1)

      Pages: 105-107

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A.2008

    • Author(s)
      Narazaki M, Segarra M, Tosato G.
    • Journal Title

      Blood 111(8)

      Pages: 4126-36

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuropilin-2 : a new molecular target for antiangiogenic and antitumor strategies.2008

    • Author(s)
      Narazaki M, Segarra M, Tosato G.
    • Journal Title

      J Natl Cancer Inst. 100(2)

      Pages: 81-3

    • Related Report
      2010 Final Research Report
  • [Journal Article] What kind of durometer is best suited for the assessment ofskin disease in systemic sclerosis? Comment on the article by Kissin et al.2008

    • Author(s)
      Kuwahara Y, Shima Y, Kawai M, Hagihara K, HiranoT, Arimitsu J, Narazaki M, Ogata A, Tanaka T, Kawase I, Ogiwara A.
    • Journal Title

      Arthritis Rheum 59(4)

      Pages: 601-601

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sulfated polysaccharides identified as inducers of neuropilin-1internalization and functional inhibition of VEGF165 and semaphorin3A.2008

    • Author(s)
      Narazaki M, Segarra M, Tosato G.
    • Journal Title

      Blood 27(4)

      Pages: 777-784

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Insufficient effect of tocilizumab on the patients with rheumatoid arthritis who have splenomegaly.2010

    • Author(s)
      楢崎雅司
    • Organizer
      The European League Against Rheumatism 2010
    • Place of Presentation
      Rome, Italia
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ligands for scavenger receptor identified as inducers of Neuropilin-1 internalization and functional inhibition of VEGF165 and Sema3A.2009

    • Author(s)
      Narazaki M, Segarra M, Tanaka T, Tosato G.
    • Organizer
      Keystone Symposia Angiogenesis and Lymphangiogenesis in Cancer
    • Place of Presentation
      Big Sky Resort, Montana, USA
    • Year and Date
      2009-01-08
    • Related Report
      2010 Final Research Report
  • [Presentation] Ligands for scavenger receptor identified as inducers of Neuropilin-1 internalization and functional inhibition of VEGF165and Sema3A.2009

    • Author(s)
      Narazaki M, Segarra M, Tanaka T, Tosato G.
    • Organizer
      Keystone Symposia Angiogenesis and Lymphangio genes is in Cancer
    • Place of Presentation
      Big Sky Resort, Montana, USA
    • Year and Date
      2009-01-08
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.osaka-u.ac.jp/pub/imed3/lab_2/page6/kurikomi.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/imed3/lab_2/page6/kurikomi.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/imed3/lab_2/page6/kurikomi.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-:u.ac.jp/pub/imed3/lab_2/page6/kurikomi.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi