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Roles of chondroitin sulfate interacting with RAGE involved in tumor and Alzheimer's disease

Research Project

Project/Area Number 25860037
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionMeijo University

Principal Investigator

Shiji Mizumoto  名城大学, 薬学部, 助教 (40443973)

Research Collaborator SUGAHARA KAZUYUKI  北海道大学, 大学院先端生命科学研究院, 名誉教授 (60154449)
YAMADA SHUHEI  名城大学, 薬学部, 教授 (70240017)
IKEGAWA SHIRO  理化学研究所, 骨関節疾患研究チーム, 主任研究員 (30272496)
MATSUMOTO NAOMICHI  横浜市立大学, 医学研究科, 教授 (80325638)
MIYAKE NORIKO  横浜市立大学, 医学研究科, 准教授 (40523494)
KOSHO TOMOKI  信州大学, 医学部附属病院, 准教授 (90276311)
Janecke Andreas  Innsbruck Medical University
Nürnberg Peter  University of Cologne
Kennerknecht Ingo  Institute of Human Genetics, Westfälische Wilhelms, Universität
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsコンドロイチン硫酸 / RAGE / 癌 / アルツハイマー病 / プロテオグリカン / ヘパラン硫酸 / 骨・皮膚疾患 / 老化 / てんかん / 糖尿病 / デルマタン硫酸
Outline of Final Research Achievements

To understand the roles of chondroitin sulfate and Receptor for Advanced Glycation-End product (RAGE) in tumor metastasis, RAGE-knockout mice were utilized for the analysis. We revealed that RAGE and chondroitin sulfate are involved in tumor metastasis and neuritogenesis based on the analyses of RAGE-knockout mice. We developed the production of recombinant RAGE using Pichia pastoris. Furthermore, we have identified a patient with short stature and bone dysplasia caused by mutation in the genes encoding chondroitin sulfate-biosynthetic glycosyltransferase.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (5 results) Remarks (1 results)

  • [Int'l Joint Research] University of Cologne/Westfalische Wilhelms Universitat(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins2016

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, Kazuyuki Sugahara
    • Journal Title

      Curr. Opin. Struct. Biol.

      Volume: 34 Pages: 35-42

    • DOI

      10.1016/j.sbi.2015.06.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor.2015

    • Author(s)
      Marina Koutsioumpa, Evangelia Poimenidi, Evangelia Pantazaka, Christina Theodoropoulou, Angeliki Skoura, Vasileios Megalooikonomou, Nelly Kieffer, Jose Courty, Shuji Mizumoto, Kazuyuki Sugahara, and Evangelia Papadimitriou.
    • Journal Title

      Molecular Cancer

      Volume: 14 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12943-015-0287-3

    • NAID

      120005906915

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia is caused by a novel mutation in B3GAT3.2015

    • Author(s)
      Birgit S. Budde, Shuji Mizumoto, Ryo Kogawa, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hohne, Kazuyuki Sugahara, Peter Nurnberg, Ingo Kennerknecht.
    • Journal Title

      Human Genetics

      Volume: in press Issue: 7 Pages: 691-704

    • DOI

      10.1007/s00439-015-1549-2

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mutations in biosynthetic enzymes for the protein linker region of chondroitin/dermatan/heparan sulfate cause skeletal and skin dysplasias2015

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, Kazuyuki Sugahara
    • Journal Title

      BioMed Res. Int.

      Volume: 2015 Pages: 861752-861752

    • DOI

      10.1155/2015/861752

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture2014

    • Author(s)
      Peraphan Pothacharoen, Sumet Najarus, Jongkolnee Settakorn, Shuji Mizumoto, Kazuyuki Sugahara, and Prachya Kongtawelert
    • Journal Title

      Glycoconjugate Journal

      Volume: 31 Issue: 3 Pages: 221-230

    • DOI

      10.1007/s10719-013-9514-6

    • NAID

      120005600748

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sulfation patterns of exogenous chondroitin sulfate affect chondrogenic differentiation of ATDC5 cells2014

    • Author(s)
      Daisuke Kawamura, Tadanao Funakoshi, Shuji Mizumoto, Kazuyuki Sugahara, and Norimasa Iwasaki
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 19 Issue: 6 Pages: 1028-1035

    • DOI

      10.1007/s00776-014-0643-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human genetic disorders and knockout mice deficient in glycosaminoglycan2014

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, and Kazuyuki Sugahara
    • Journal Title

      BioMed Research International

      Volume: 2014 Pages: 495764-495764

    • DOI

      10.1155/2014/495764

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Human genetic disorders caused by defective genes encoding biosynthetic enzymes for sulfated glycosaminoglycans2013

    • Author(s)
      Shuji Mizumoto, Shiro Ikegawa, andKazuyuki Sugahara
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 16 Pages: 10953-10961

    • DOI

      10.1074/jbc.r112.437038

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycosaminoglycans are functional ligands for Receptor for Advanced Glycation End-products (RAGE) in tumors2013

    • Author(s)
      Mizumoto, S., and Sugahara, K.
    • Journal Title

      FEBS Journal

      Volume: 280 Issue: 10 Pages: 2462-2470

    • DOI

      10.1111/febs.12156

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduction of Chondroitin 4-<i>O</i>-Sulfotransferase-1 Expression Causes Costello Syndrome2013

    • Author(s)
      Shuji Mizumoto
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 25 Issue: 142 Pages: 87-89

    • DOI

      10.4052/tigg.25.87

    • NAID

      10031190623

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines2013

    • Author(s)
      Shuji Mizumoto, Duriya Fongmoon, Kazuyuki Sugahara
    • Journal Title

      Glycoconjugate Journal

      Volume: in press Issue: 6 Pages: 619-632

    • DOI

      10.1007/s10719-012-9463-5

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutations in B3GALT6 which Encodes a Glycosaminoglycan Linker Region Enzyme Cause a Spectrum of Skeletal and Connective Tissue Disorders2013

    • Author(s)
      Masahiro Nakajima, Shuji Mizumoto et al.
    • Journal Title

      American Journal of Human Genetics

      Volume: in press Issue: 6 Pages: 927-934

    • DOI

      10.1016/j.ajhg.2013.04.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome2013

    • Author(s)
      Thomas Muller, Shuji Mizumoto, Indrajit Suresh, Yoshie Komatsu, Julia Vodopiutz, Munis Dundar, Volker Straub, Arno Lingenhel, Andreas Melmer, Silvia Lechner, Johannes Zschocke, Kazuyuki Sugahara, Andreas R Janecke
    • Journal Title

      Human Molecular Genetics

      Volume: 22 Issue: 18 Pages: 3761-3772

    • DOI

      10.1093/hmg/ddt227

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical and radiographic features of the autosomal recessive form of brachyolmia caused by PAPSS2 mutations2013

    • Author(s)
      Aritoshi Iida*, Pelin Ozlem Simsek-Kiper*, Shuji Mizumoto*, Touma Hoshino, Nursel Elcioglu, Eva Horemuzova, Stefan Geiberger, Gozde Yesil, Hulya Kayserili, Gulen Eda Unite, Koray Boduroglu, Shigehiko Watanabe, Hirofumi Ohashi, Yasemin Alanay, Kazuyuki Sugahara, Gen Nishimura, Shiro Ikegawa (*equal contribution)
    • Journal Title

      Human Mutation

      Volume: 34 Issue: 10 Pages: 1381-1386

    • DOI

      10.1002/humu.22377

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Detection of the degradation activities of chondroitin sulfate and hyaluronan in mouse brain as well as cultured cell lines2016

    • Author(s)
      ◯Shuji Mizumoto, Tomomasa Yamanaka, Sae Nagai, and Shuhei Yamada
    • Organizer
      The 3rd International Symposium on Glyco-Neuroscience
    • Place of Presentation
      淡路夢舞台国際会議場(淡路)
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グリコサミノグリカンの生合成に関わるグルクロン酸転移酵素-Iの変異によるインドネシアのニアス島で見つかった骨疾患2015

    • Author(s)
      ◯Shuji Mizumoto, Birgit S. Budde, Ryo Kogawa, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hohne, Kazuyuki Sugahara, Peter Nurnberg, Ingo Kennerknecht
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会・合同大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低身長を特徴とする遺伝性骨疾患はグリコサミノグリカンの生合成に関わるグルクロン酸転移酵素-Iの変異によって引き起こされる2015

    • Author(s)
      ◯水本秀二、Birgit S. Budde、古川諒、Peter Nurnberg、Ingo Kennerknecht、菅原一幸
    • Organizer
      糖鎖科学中部拠点 第12回若手の力フォーラム
    • Place of Presentation
      名城大学(名古屋)
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Loss-of-function mutation of glucuronyltransferase-I causes skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia2015

    • Author(s)
      ◯Shuji Mizumoto, Birgit S. Budde, Ryo Kogawa, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hahne, Kazuyuki Sugahara, Peter Nurnberg, Ingo Kennerknecht
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Ewha Womans University (Seoul, Korea)
    • Year and Date
      2015-08-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グリコサミノグリカンの生合成に関わるグルクロン酸転移酵素-Iの新規変異による骨疾患の糖鎖生物学的研究2015

    • Author(s)
      ○水本秀二, Birgit S. Budde, 古川諒, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hohne, 菅原一幸, Peter Nurnberg, Ingo Kennerknecht
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] コンドロイチン・デルマタン・ヘパラン硫酸の生合成に関わるグルクロン酸転移酵素-Iの変異(P140L)による骨疾患の糖鎖生物学的研究2015

    • Author(s)
      ○水本秀二, Birgit S. Budde, 古川諒, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hohne, 菅原一幸, Peter Nurnberg, Ingo Kennerknecht
    • Organizer
      第79回日本生化学会中部支部例会
    • Place of Presentation
      信州大学松本キャンパス(松本)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Spondyloepimetaphyseal dysplasia and Ehlers-Danlos syndrome caused by mutations of glycosaminoglycan biosynthetic enzymes, GalT-II and DS-epimerase2014

    • Author(s)
      Shuji Mizumoto, Masahiro Nakajima, Thomas Muller Noriko Miyake, Ryo Kogawa, Yoshie Komatsu, Naomichi Matsumoto, Andreas R Janecke, Shiro Ikegawa, Kazuyuki Sugahara
    • Organizer
      Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research
    • Place of Presentation
      Hilton Hotel (Hawaii, USA)
    • Year and Date
      2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] プロテオグリカン糖側鎖の生合成異常による遺伝性の骨・皮膚疾患2014

    • Author(s)
      水本秀二
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会議場(京都)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] PAPS合成酵素2の変異は常染色体劣性型短脊柱症を引き起こす2014

    • Author(s)
      水本秀二, 飯田有俊, Pelin Ozlem Simsek-Kiper, 星野冬馬, Nursel Elcioglu, Eva Horemuzova, Stefan Geiberger, Gozde Yesil, Hulya Kayserili, Gulen Eda Utine, Koray Boduroglu, 渡邉成彦, 大橋博文, Yasemin Alanay, 西村玄, 池川志郎, 菅原一幸
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋大学(名古屋)
    • Year and Date
      2014-08-11
    • Related Report
      2014 Research-status Report
  • [Presentation] グリコサミノグリカンの生合成異常による遺伝性の骨・皮膚疾患2014

    • Author(s)
      水本秀二
    • Organizer
      第22回PGフォーラム(第46回日本結合組織学会学術大会・第61回マトリックス研究会大会・合同学術大会)
    • Place of Presentation
      ウインク愛知(名古屋)
    • Year and Date
      2014-06-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] コンドロイチン硫酸/デルマタン硫酸の生合成に関わる酵素の変異による骨・皮膚疾患の糖鎖生物学的研究

    • Author(s)
      ○水本秀二, 中島正宏, Thomas Muller, 三宅紀子, Indrajit Suresh, 古川諒, 小松由枝, 松本直通, Andreas R Janecke, 池川志郎, 菅原一幸
    • Organizer
      日本生化学会北海道支部 支部例会第50回記念大会
    • Place of Presentation
      北海道大学医学部(札幌)
    • Related Report
      2013 Research-status Report
  • [Presentation] グリコサミノグリカンの生合成に関わる酵素の新規変異による脊椎骨端骨幹端異形成症とエーラス・ダンロス症候群の糖鎖生物学的研究

    • Author(s)
      ○水本秀二, 中島正宏, Thomas Muller, 三宅紀子, Indrajit Suresh, 古川諒, 小松由枝, 松本直通, Andreas R Janecke, 池川志郎, 菅原一幸
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪国際交流センター(大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] PAPS合成酵素2の変異によって引き起こされる常染色体劣性型短脊柱症

    • Author(s)
      ○水本秀二, 飯田有俊, Pelin Ozlem Simsek-Kiper, 星野冬馬, Nursel Elcioglu, Eva Horemuzova, Stefan Geiberger, Gozde Yesil, Hulya Kayserili, Gulen Eda Utine, Koray Boduroglu, 渡邉成彦, 大橋博文, Yasemin Alanay, 西村玄, 池川志郎, 菅原一幸
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本大学工学部(熊本)
    • Related Report
      2013 Research-status Report
  • [Book] Chondroitin Sulfate In Encyclopedia of Polymeric Nanomaterials2015

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, Shuhei Yamada
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] ヘパラン硫酸 In 糖鎖の新機能開発・応用ハンドブック~創薬・医療からヘルスケアまで~2015

    • Author(s)
      水本秀二、菅原一幸
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2015 Annual Research Report
  • [Book] グリコサミノグリカン・プロテオグリカンの分解 In 糖鎖の新機能開発・応用ハンドブック~創薬・医療からヘルスケアまで~2015

    • Author(s)
      山田修平、水本秀二、菅原一幸
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2015 Annual Research Report
  • [Book] Encyclopedia of Polymeric Nanomaterials2015

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, Shuhei Yamada
    • Total Pages
      2500
    • Publisher
      Springer-Verlag
    • Related Report
      2014 Research-status Report
  • [Book] Carbohydrate (N-acetyl-D-galactosamine 4-O) sulfotransferase 14 (CHST14) In Handbook of Glycosyltransferases and Related Gene2014

    • Author(s)
      Tomoki Kosho, Shuji Mizumoto, Kazuyuki Sugahara
    • Publisher
      Springer
    • Related Report
      2013 Research-status Report
  • [Remarks] 名城大学薬学部病態生化学研究室ホームページ

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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