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An investigation for optimal signal crosstalk in heparin binding growth factor promoting neurogenesis

Research Project

Project/Area Number 15K09326
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

Arikawa-Hirasawa Eri  順天堂大学, 医学(系)研究科(研究院), 教授 (50245718)

Co-Investigator(Renkei-kenkyūsha) KIMATA Koji  愛知医科大学, 大学院医学研究科, 特任教授 (10022641)
SASAKI Takako  大分大学, 大学院医学研究科, 助教 (30133193)
KEREVER Aurelien  順天堂大学, 大学院医学研究科, 助教 (70623594)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヘパラン硫酸プロテオグリカン / ヘパリン親和性増殖因子 / 成体神経新生 / 糖鎖 / 硫酸化 / 細胞外マトリックス / ヘパラン硫酸プロテオグリ カン / 肝細胞増殖因子(HGF) / ヘパラン硫酸プ ロテオグリカン
Outline of Final Research Achievements

Heparin affinity growth factor group is expected as one of therapeutic targets for neurodegenerative diseases typified by hepatocyte growth factor (HGF), but there are many problems to be solved to realize clinical application. In this study, we aim to develop an adult neurogenesis control method by targeting heparan sulfate proteoglycan (HSPG) in the extracellular matrix and optimizing GF activity localization and "signal crosstalk" with other heparin affinity growth factors. Modification of sugar chain was considered important for preparation of heparin affinity growth factor / heparan sulfate chain typified by FGF - 2 which controls adult neurogenesis. We proceeded with disaccharide analysis using samples of the adventitial neurogenic region, the subventricular zone and the hippocampus, and showed characteristics of sugar chain modification such as sulfation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 2 results,  Open Access: 3 results) Presentation (19 results) (of which Int'l Joint Research: 7 results)

  • [Journal Article] Heparan Sulfate Alterations in Extracellular Matrix Structures and FGF-2 Signaling Impairment in the Aged Neurogenic Niche.2017

    • Author(s)
      Yamada T, Kerever A, Yoshimura Y, Suzuki Y, Nonaka R, Higashi K, Toida T, Mercier F, Arikawa-Hirasawa E.
    • Journal Title

      J Neurochem.

      Volume: 142 Issue: 4 Pages: 534-544

    • DOI

      10.1111/jnc.14081

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perlecan is required for the chondrogenic differentiation of synovial mesenchymal cells through regulation of Sox9 gene expression2017

    • Author(s)
      Sadatsuki R, Kaneko H, Futami I, Kinoshita M, Nonaka R, Culley KL, Otero M, Hada S, Goldring MB, Yamada Y, Kaneko K, Arikawa-Hirasawa E, Ishijima M
    • Journal Title

      J Orthop Res

      Volume: 35 Issue: 4 Pages: 837-46

    • DOI

      10.1002/jor.23318

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Understanding microstructure of he brain by comparison of neurite orientation dispersion and density imaging (NODDI) with transparent mouse brain2017

    • Author(s)
      Kanako Sato, Aurelien Kerever, Koji Kamagata,Kohei Tsuruta,Ryusuke Irie, Kazuhiko Tagawa,Hitoshi Okazawa, Eri Arikawa-Hirasawa, Nobuhiro Nitta,Ichio Aoki and Shigeki Aoki
    • Journal Title

      Acta Radiologica

      Volume: 6(4) Pages: 1-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Histological Validation of Diffusion Tensor MRI with Two-Photon Microscopy of Cleared Mouse Brain.2016

    • Author(s)
      Kamagata K, Kerever A, Yokosawa S, Otake Y, Ochi H, Hori M, Kamiya K, Tsuruta K, Tagawa K, Okazawa H, Aoki S, Arikawa-Hirasawa E.
    • Journal Title

      Magn Reson Med Sci.

      Volume: 15(4) Pages: 416-421

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Peptides Derived from the C-terminal Domain of Fibulin-7 Active for Endothelial Cell Adhesion and Tube Formation Disruption.2016

    • Author(s)
      de Vega S, Hozumi K, Suzuki N, Nonaka R, Seo E, Takeda A, Ikeuchi T, Nomizu M, Yamada Y, Arikawa-Hirasawa E
    • Journal Title

      Biopolymers.

      Volume: pub Issue: 2 Pages: 184-195

    • DOI

      10.1002/bip.22754

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle.2015

    • Author(s)
      Ning L, Xu Z, Furuya N, Nonaka R, Yamada Y, Arikawa-Hirasawa E.
    • Journal Title

      Matrix Biol.

      Volume: 48 Pages: 26-35

    • DOI

      10.1016/j.matbio.2015.08.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fractone aging in the subventricular zone of the lateral ventricle.2015

    • Author(s)
      Kerever A, Yamada T, Suzuki Y, Mercier F, Arikawa-Hirasawa E.
    • Journal Title

      J Chem Neuroanat

      Volume: 66-67 Pages: 52-60

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A missense mutation in domain III in HSPG2 in Schwartz-Jampel syndrome compromises secretion of perlecan into the extracellular space.2015

    • Author(s)
      Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K.
    • Journal Title

      Neuromuscul Disord.

      Volume: 25(8) Issue: 8 Pages: 667-71

    • DOI

      10.1016/j.nmd.2015.05.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] See-through Brains and Diffusion Tensor MRI Clarified Fiber Connections: A Preliminary Microstructural Study in a Mouse with Callosal Agenesis2015

    • Author(s)
      Kerever A, Kamagata K, Yokosawa S, Otake Y, Ochi H, Yamada T, Hori M, Kamiya K, Nishikori A, Aoki S, Arikawa-Hirasawa E.
    • Journal Title

      Magnetic Resonance in Medical Sciences

      Volume: 14 Issue: 2 Pages: 159-162

    • DOI

      10.2463/mrms.2014-0142

    • NAID

      130005069924

    • ISSN
      1347-3182, 1880-2206
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Perlecan deficiency causes endothelial dysfunction by reducing the expression of endothelial nitric oxide synthase.2015

    • Author(s)
      Risa Nonaka, Takafumi Iesaki, Susana de Vega, Hiroyuki Daida, Takao Okada, Takako Sasaki, and Eri Arikawa-Hirasawa
    • Journal Title

      Physiological Reports

      Volume: 3(1) Issue: 1 Pages: e12272-e12272

    • DOI

      10.14814/phy2.12272

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 細胞脳組織におけるニューロスフィア培養―細胞外マトリックスが加齢性の神経新生減弱に果たす役割の解明を目指して2017

    • Author(s)
      吉村祐輔、曺叡智、鈴木佑治、オーレリアン・ケレベール・平澤(有川)恵理
    • Organizer
      第49回日本結合組織学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The structural and compositional changes of chondroitin sulfate in the aged hippocampus.2016

    • Author(s)
      Yuji Suzuki, Aurelien Kerever, Taihei Yamada, Yusuke Yoshimura, Kyohei Higashi, Toshihiko Toida, Nobutaka Hattori, Eri Arikawa-Hirasawa.
    • Organizer
      Gordon Research Conference: Proteoglycans
    • Place of Presentation
      NH Andover, USA
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Age-Associated Changes in Heparan Sulfate Structures Impair FGF-2 Signaling in Neurogenesis2016

    • Author(s)
      Taihei Yamada, Aurelien Kerever, Yusuke Yoshimura, Yuji Suzuki, Kyouhei Higashi, Toshihiko Toida and Eri Arikawa-Hirasawa
    • Organizer
      Gordon Research Conference: Proteoglycans
    • Place of Presentation
      NH Andover, USA
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] mmunohistochemical analysis of ECM structures in postnatal brain development of a mouse model of autism2016

    • Author(s)
      Aurelien Kerever , Eri Arikawa-Hirasawa
    • Organizer
      Gordon Research Conference: Proteoglycans
    • Place of Presentation
      NH Andover, USA
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of perlecan in lipid dynamism. Gordon Research Conference.2016

    • Author(s)
      Yuri Yamashita, Risa Nonaka, Nobutaka Hattori, Eri Arikawa-Hirasawa.
    • Organizer
      Gordon Research Conference: Proteoglycans
    • Place of Presentation
      NH Andover, USA
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス成体神経新生領域の老化におけるヘパラン硫酸鎖の変化2016

    • Author(s)
      吉村祐輔, 山田泰平, ケレベールオーレリアン, 東恭平, 戸井田敏彦, 服部信孝, 平澤恵理
    • Organizer
      57回日本神経学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Different visualization of transparent brain by MR imaging2016

    • Author(s)
      青木茂樹, 鎌形康司, Aurelien Kerever , 佐藤香菜子, 堀正明, 岡澤均, 平澤恵理
    • Organizer
      57回日本神経学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Quantitative Histological Validation of Diffusion Tensor MRI by Two-Photon Microscopy of Cleared Mouse Brain2016

    • Author(s)
      鎌形康司, Kerever Aurelien, 横沢俊, 堀正明, 鶴田航平, 田川一彦, 岡澤均, 平澤恵理, 青木茂樹
    • Organizer
      第18回日本ヒト脳機能マッピング学会
    • Place of Presentation
      京都大学桂キャンパス 船井哲良記念講堂 京都
    • Year and Date
      2016-03-07
    • Related Report
      2015 Research-status Report
  • [Presentation] Sulfated glycosaminoglycans analysis in the aged mouse subventricular zone2016

    • Author(s)
      Yamada T, Kerever A, Toida T, Higashi K, Arikawa-Hirasawa E.
    • Organizer
      ” The 3rd International Symposium on Glyco- Neuroscience
    • Place of Presentation
      Yumebutai Awaji city, Hyogo
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of chondroitin sulfate in the aged mouse hippocampus2016

    • Author(s)
      Suzuki Y, Kerever A, Toida T, Higashi K, Arikawa-Hirasawa E.
    • Organizer
      ” The 3rd International Symposium on Glyco- Neuroscience
    • Place of Presentation
      Yumebutai Awaji city, Hyogo
    • Year and Date
      2016-01-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Extracellular matrix aging in the mouse hippocampus2015

    • Author(s)
      Yuji Suzuki, Aurelien Kerever, Taihei Yamada, Eri Arikawa-Hirasawa
    • Organizer
      38th meeting of the Japanese neuroscience Society
    • Place of Presentation
      神戸国際会議場 神戸 兵庫
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Schwartz-Jampel 症候群の原因遺伝子、パールカンの筋オートファジーへの関与2015

    • Author(s)
      平澤 恵理、寧 亮、古屋 徳彦、野中 里紗、服部 信孝
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟コンベンションセンター)新潟
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Aging of the extracellular matrix structure fractone in the mouse subventricular zone2015

    • Author(s)
      Aurelien Kerever, Taihei Yamada, and Eri Arikawa-Hirasawa
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Sugar chain modification in the aged mouse hippocampus2015

    • Author(s)
      Yuji Suzuki, Aurelien Kerever, Taihei Yamada, Eri Arikawa-Hirasawa.
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Aging Associated Changes of Extracellular Matrix Structures Impairs FGF-2 Signaling in Aged Subventricular Zone2015

    • Author(s)
      Taihei Yamada, Aurelien Kerever, Yuji Suzuki and Eri Arikawa-Hirasawa.
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Perlecan inhibits the autophagic process via the Akt/mTORC1 signaling pathway in mouse soleus muscle2015

    • Author(s)
      Liang Ninga, Zhuo Xua, †, Norihiko Furuyab,c, Risa Nonakaa, Yoshihiko Yamadad, Eri Arikawa-Hirasawa
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 50.大動脈内皮のeNOS遺伝子発現の活性化におけるパールカンの役割2015

    • Author(s)
      野中 里紗、家崎 貴史、Susana de Vega1、佐々木 隆子、山田 吉彦,
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 安定同位体標識コラーゲンを用いた血中、尿中のコラーゲン由来因子の高精度定量分析2015

    • Author(s)
      多賀 祐喜、石島 旨章、平澤 (有川) 恵理田中 啓友、水野 一乘、楠畑 雅、服部 俊治
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      コクヨホール 東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Synthetic Peptides Derived from the C-terminal Fibulin-type Domain of Fibulin-7: Role in Endothelial Cell Adhesion2015

    • Author(s)
      S. de Vega, K. Hozumi, N. Suzuki, R. Nonaka, E. Seo, A. Takeda, T. Ikeuchi, M. Nomizu, Y. Yamada, and E. Arikawa-Hirasawa
    • Organizer
      第47回結合組織学会学術大会
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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