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Regulatory mechanisms for the activity of heparin-binding ligands through heparan sulfate proteoglycan with the specific sufation patterns

Research Project

Project/Area Number 20570113
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionAichi Medical University

Principal Investigator

HABUCHI Hiroko  Aichi Medical University, 客員研究員 (90329821)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖鎖生物 / ヘパラン硫酸 / 硫酸転移酵素 / 細胞増殖因子 / 遺伝子改変マウス / プロテオグリカン / マスト細胞 / 糖鎖生物学 / プロテアーゼ / 酵素 / シグナル伝達
Research Abstract

HS octasaccharide library was produced by recombinant HS6ST and HS2ST. FGF-2-dependent signaling was inhibited by 2-O-sulfated HS octasaccharide, whereas the inhibition of FGF-4-dependent signaling required 2-O- and 6-O-sulfated HS octasaccharide. Mast cells derived from HS2ST and HS6ST-1 -2 double knockout mice fetal skin produced 2-O-sulfate- and 6-O-sulfate-deficient heparin, respectively. The deposit of three mast cell-specific proteases were distinctly inhibited in the each mutated mast cells. the collaborated studies with Bulow elucidated that the mutated HS6ST1 gene was involved in patients with idiopathic hypogonadotrophic hypogonadism (IHH).

Report

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

    (27 results)

All 2011 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (4 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Heparan Sulfate 6-O-sulfotransferase 1 (HS6ST1), a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism2011

    • Author(s)
      Tornberg J, Sykiotis G.P., Habuchi H, Pitteloud N, Bulow H.E., et al
    • Journal Title

      Proc.Natl.Acad.Sci accepted

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preparation of chondroitin sulfate libraries containing disulfated disaccharide units and inhibition of thrombin by these chondroitin sulfates.2010

    • Author(s)
      Numakura M, Kusakabe N, Ishige K, Ohtake-Niimi S, Habuchi H, Habuchi O.
    • Journal Title

      Glycoconj J. 27

      Pages: 479-489

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mice deficient in N-acetylgalactosamine 4-sulfate 6-O--sulfotransferase are unable to synthesize chondroitin/dermatan sulfate containing N-acetylgalactosamine 4,6-bissulfate residues and exhibit decreased protease activity in bone marrow-derived mast cells2010

    • Author(s)
      Ohtake-Niimi S, Kondo S, Ito T, Kakehi S, Ohta T, Habuchi H, Kimata K, Habuchi O.
    • Journal Title

      J Biol Chem 285

      Pages: 20793-20805

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional analysis of chick heparan sulfate 6-O-sulfotransferases in limb bud development.2010

    • Author(s)
      Kobayashi T, Habuchi H, Nogami K, Ashikari-Hada S, Tamura K, Ide H, Kimata K.
    • Journal Title

      Dev Growth Differ. 52

      Pages: 146-156

    • NAID

      10027563610

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance.2010

    • Author(s)
      Stanford KI, Wang L, Castagnola J, Habuchi H, Esko JD, et al
    • Journal Title

      J Biol Chem. 285

      Pages: 286-294

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preparation of chondroitin sulfate libraries containing disulfated disaccharide units and inhibition of thrombin by these chondroitin sulfates.2010

    • Author(s)
      Numakura Habuchi H, Habuchi O, et al
    • Journal Title

      Glycoconj J.

      Volume: vol.27 Pages: 479-489

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mice deficient in N-acetylgalactosamine 4-sulfate 6-o-sulfotransferase are unable to synthesize chondroitin/dermatan sulfate containing N-acetylgalactosamine 4, 6-bissulfate residues and exhibit decreased protease activity in bone marrow-derived mast cells.--2010

    • Author(s)
      Ohtake-Niimi Habuchi H, Habuchi O, et al
    • Journal Title

      J.Biol.Chem.

      Volume: vol.285 Pages: 20793-20805

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance2010

    • Author(s)
      Stanford KI, Habuchi H., et al
    • Journal Title

      J Biol Chem. 285

      Pages: 286-294

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional analysis of chick heparan sulfate 6-O-sulfotransferases in limb bud development2010

    • Author(s)
      Kobayashi T, Habuchi H., et al
    • Journal Title

      Dev Growth Differ. 52

      Pages: 146-156

    • NAID

      10027563610

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific inhibition of FGF-2 signaling with 2-O-sulfated octasaccharides of heparan sulfate2009

    • Author(s)
      Ashikari-Hada S, Habuchi H, Sugaya N, Kobayashi T, Kimata K.
    • Journal Title

      Glycobiology 19

      Pages: 644-654

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific inhibition of FGF-2 signaling with 2-O-sulfated octasaccharides of heparan sulfate2009

    • Author(s)
      Ashikari-Hada S, Habuchi H., et al
    • Journal Title

      Glycobiology 19

      Pages: 644-654

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific inhibition of FGF-2 signaling with 2-O-sulfated oligosaccharides of heparan sulfate2009

    • Author(s)
      Ashikari-Hada S., Habuchi H., et al
    • Journal Title

      Glycobiology (in press)

      Pages: 11-11

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 6-O-sulfation of heparan sulfate differentially regulates various fibroblast growth factor-dependent signalings in culture.2008

    • Author(s)
      Sugaya N, Habuchi H, Nagai N, Ashikari-Hada S, Kimata K.
    • Journal Title

      J Biol Chem. 283

      Pages: 10366-10376

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ヘパラン硫酸プロテオグリカンの器官形成と疾患における役割2008

    • Author(s)
      羽渕弘子、木全弘治
    • Journal Title

      生体の科学 59

      Pages: 83-91

    • Related Report
      2010 Final Research Report
  • [Journal Article] 6-O-sulfation of Heparan Sulfate Differentially Regulates various Fibroblast Growth Factor-depend2008

    • Author(s)
      Sugaya N., Habuchi H., Kimata K., et al
    • Journal Title

      J. Biol. Chem. 283

      Pages: 10366-10376

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ヘパラン硫酸プロテオグリカンの器官形成と疾患における役割2008

    • Author(s)
      羽渕弘子 木全弘治
    • Journal Title

      生体の科学 59

      Pages: 83-91

    • Related Report
      2008 Annual Research Report
  • [Presentation] 二糖二硫酸単位を含むコンドロイチン硫酸ライブラリーの調製とこれらのコンドロイチン硫酸によるトロンビン活性の阻害2010

    • Author(s)
      沼倉真理緒、日下部教子、石毛和也、大竹-新美しおり、羽渕弘子、羽渕脩躬
    • Organizer
      BMB2010(第83会日本生化学会大会)
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-08
    • Related Report
      2010 Final Research Report
  • [Presentation] preparation of chondroitin sulfate libraries containing disulfated disaccharide.---2010

    • Author(s)
      沼倉、日下部石毛、大竹、羽渕、羽渕
    • Organizer
      BMB2010(第83回日本生化学会大会)
    • Place of Presentation
      神戸ポートアイランド((兵庫県)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 培養マスト細胞におけるヘパリンの2-硫酸化と2-硫酸化ヘパリンの機能2009

    • Author(s)
      羽渕弘子、羽渕脩躬、木全弘治
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2009-10-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 培養マスト細胞におけるヘパリンの2-硫酸化と2-硫酸化ヘパリンの機能2009

    • Author(s)
      羽渕弘子, 羽渕脩躬, 木全弘治, ら
    • Organizer
      日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Book] Prog Mol Biol Transl Sci.(93)(Mice deficient in heparan sulfate 6-O-sulfotransferase-1.)2010

    • Author(s)
      Habuchi H, Kimata K.
    • Publisher
      Elsevier Inc.
    • Related Report
      2010 Final Research Report
  • [Book] Prog Mol Biol Tansl. Sci. Mice deficient in heparan sulfate 6-O-sulfotransferase-1.2010

    • Author(s)
      Habuchi H, Kimata K
    • Publisher
      Elsevier Inc
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.aichi-med-u.ac.jp/institute/outline/sentanigaku.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.aichi-med-u.ac.jp/

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] クラミジア感染症処置剤2010

    • Inventor(s)
      藪下廣光、羽渕弘子、木全弘治
    • Industrial Property Rights Holder
      生化学工業株式会社
    • Acquisition Date
      2010-11-26
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] ノックアウト動物2009

    • Inventor(s)
      木全弘治、羽渕弘子、佐藤尚子
    • Industrial Property Rights Holder
      生化学工業株式会社
    • Industrial Property Number
      2009-193909
    • Filing Date
      2009-08-25
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 硫酸基転移酵素及びそれをコードするDNA2008

    • Inventor(s)
      羽渕弘子、田中雅之、木全弘治
    • Industrial Property Rights Holder
      生化学工業株式会社
    • Acquisition Date
      2008-12-15
    • Related Report
      2010 Final Research Report

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

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