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Elucidation of the Intracellular PGE2 receptor Function with Appliance of Optical Functional Nanoparticle

Research Project

Project/Area Number 15K14966
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pharmacology in pharmacy
Research InstitutionNihon University

Principal Investigator

ITO Yoshihisa  日本大学, 薬学部, 教授 (50151551)

Co-Investigator(Kenkyū-buntansha) 須川 晃資  日本大学, 理工学部, 准教授 (40580204)
小菅 康弘  日本大学, 薬学部, 准教授 (70383726)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsPGE2 / 運動ニューロン / グラフェン / 神経突起 / ALS / 細胞分化 / 突起進展 / ナノグラフェン / パッチクランプ法 / PGE2受容体 / ナノ粒子 / 細胞毒性
Outline of Final Research Achievements

Prostaglandin E2 (PGE2) is a lipid mediator that plays important roles in various physiological and pathophysiological processes in the brain and spinal cord. We found that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the PGE2 receptor EP2 subtype, and that the Gs protein-coupled cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells, a mouse motor neuron-like cell line. Moreover, we demonstrated the expression of EP2 in motor neurons is selectively increased in the lumbar spinal cord of ALS model mice at the symptomatic stage. Our in vitro approach using differentiated-NSC-34 cells has shown that PGE2 is involved in up-regulation of EP2 in these cells, and that PGE2-induced EP2 up-regulation in motor neurons may exacerbate the neuronal damage in ALS.

Report

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

    (21 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.2018

    • Author(s)
      Kosuge Y, Miyagishi H, Yoneoka Y, Yoneda K, Nango H, Ishige K, Ito Y.
    • Journal Title

      Neurochem Int.

      Volume: 印刷中 Pages: 132-139

    • DOI

      10.1016/j.neuint.2017.06.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-342017

    • Author(s)
      Nango, Hiroshi; Kosuge, Yasuhiro; Miyagishi, Hiroko; Sugawa, Kosuke; Ito, Yoshihisa; Ishige, Kumiko
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 135 Issue: 2 Pages: 64-71

    • DOI

      10.1016/j.jphs.2017.09.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased Expression of 15-Hydroxyprostaglandin Dehydrogenase in Spinal Astrocytes During Disease Progression in a Model of Amyotrophic Lateral Sclerosis2017

    • Author(s)
      Miyagishi H, Kosuge Y, Takano A, Endo M, Nango H, Yamagata-Murayama S, Hirose D, Kano R, Tanaka Y, Ishige K, Ito Y.
    • Journal Title

      Cell Mol Neurobiol

      Volume: 37 Issue: 3 Pages: 445

    • DOI

      10.1007/s10571-016-0377-9

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Motor Neuron Prostaglandin E2 EP3 Receptor Isoform in a Mouse Model of Amyotrophic Lateral Sclerosis2015

    • Author(s)
      Kosuge Y, Miyagishi H, Shinomiya T, Nishiyama K, Suzuki S, Osada N, Ishige K, Okubo M, Kawaguchi M, Ito Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 12 Pages: 1964-1968

    • DOI

      10.1248/bpb.b15-00418

    • NAID

      130005112645

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 運動ニューロン様株化細胞NSC-34におけるPGE2前処置はEP2の発現増加を介してPGE2誘発細胞死を増強する2018

    • Author(s)
      南郷 拓嗣, 小菅 康弘, 石毛 久美子, 伊藤 芳久
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 運動神経様株化細胞NSC-34におけるProstaglandin E2による神経突起伸長の促進2017

    • Author(s)
      南郷拓嗣、小菅康弘、須川晃資、Seikwan Oh、伊藤芳久、石毛久美子
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎、長崎)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] NSC-34におけるPGE2による突起伸長機構に関する研究2017

    • Author(s)
      南郷 拓嗣, 小菅 康弘, 伊藤 芳久, 石毛 久美子
    • Organizer
      第19回応用薬理シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] NSC-34におけるPGE2による細胞分化に関する研究2017

    • Author(s)
      南郷 拓嗣、小菅 康弘、伊藤 芳久、石毛 久美子
    • Organizer
      第1回下総薬理学研究会 2017年6月24日
    • Related Report
      2017 Annual Research Report
  • [Presentation] 近赤外光応答金ナノ粒子/ナノ酸化グラフェン複合体を用いた光熱治療材料の機能解析2017

    • Author(s)
      徳田 亨、須川 晃資、大月 穣
    • Organizer
      第68回コロイドおよび界面化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ナノ酸化グラフェン修飾金ナノスターの作製と光学特性解析2016

    • Author(s)
      徳田 亨, 須川 晃資, 小菅 康弘, 伊藤 芳久, 大月 穣
    • Organizer
      第6回CSJ化学フェスタ2016
    • Place of Presentation
      タワーホール船堀(東京、江戸川)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Prostaglandin E2 promotes neurite outgrowth via EP2-cAMP signaling pathway in NSC-34 cells, a motor neuron-like cell line.2016

    • Author(s)
      Hiroshi Nango, Yasuhiro Kosuge, Kumiko Ishige, Yoshihisa Ito
    • Organizer
      The Society for Neuroscience's 46th annual meeting, Neuroscience 2016
    • Place of Presentation
      San Diego Convention Center, CA (USA)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] PEG修飾ナノグラフェンを基軸とするpH応答性ドラックデリバリーキャリアーの機能性解析2016

    • Author(s)
      徳田 亨, 須川 晃資, 小菅 康弘, 伊藤 芳久, 大月 穣
    • Organizer
      第67回コロイドおよび界面化学討論会
    • Place of Presentation
      北海道教育大学旭川校(北海道、旭川)
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
  • [Presentation] Synthesis and Characterization of Nanographene Oxide-Modified Gold Nanostars2016

    • Author(s)
      Kyo Tokuda, Kosuke Sugawa, Yasuhiro Kosuge, Yoshihisa Ito, Joe Otsuki
    • Organizer
      KJF-ICOMEP2016
    • Place of Presentation
      ACROS Fukuoka (FUKUOKA, FUKUOKA)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 沖縄産植物由来エキスを用いた筋萎縮性側索硬化症(ALS)治療薬の開発2016

    • Author(s)
      小菅康弘、石毛久美子、伊藤芳久
    • Organizer
      第18回 応用薬理シンポジウム
    • Place of Presentation
      名古屋大学 医学部(愛知、名古屋)
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
  • [Presentation] PGE2はPGE2-cAMPシグナル伝達系を介して運動ニューロン様株化細胞NSC-34の神経突起伸長を促進する2016

    • Author(s)
      南郷拓嗣 小菅康弘 石毛久美子 伊藤芳久
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Functional evaluation of PEG-modified nanographene as a drug delivery career2016

    • Author(s)
      TOKUDA, Kyo; SUGAWA, Kosuke; KOSUGE, Yasuhiro; OTSUKI, Joe; ITO, Yoshihisa
    • Organizer
      日本化学会 第96春季年会
    • Place of Presentation
      同志社大学(京都・京田辺)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 抗腫瘍性抗生物質Mithramycinの筋萎縮性側索硬化症治療薬としての可能性2016

    • Author(s)
      兼古絵里菜、小菅 康弘、鈴木 里実、南郷 拓嗣、石毛久美子、伊藤 芳久
    • Organizer
      第134回日本薬理学会関東部会
    • Place of Presentation
      国際医療福祉大学薬学部(栃木、大田原)
    • Related Report
      2016 Research-status Report
  • [Presentation] 低分子化合物を用いた新規筋萎縮性側索硬化症治療薬の開発2015

    • Author(s)
      伊藤芳久, 小菅康弘, 石毛久美子
    • Organizer
      第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
    • Place of Presentation
      タワーホール船堀(東京・船堀)
    • Year and Date
      2015-09-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 筋萎縮性側索硬化症(ALS)モデルマウスにおけるprostaglandin E2代謝・ 輸送系の変動とその分布2015

    • Author(s)
      高野あゆみ, 小菅康弘, 宮岸寛子, 遠藤愛美, 石毛久美子, 伊藤芳久
    • Organizer
      第132回日本薬理学会関東部会
    • Place of Presentation
      明海大学(千葉・浦安)
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report
  • [Book] わかりやすい薬理学-薬の効くプロセス-(第11版)2017

    • Author(s)
      伊藤 芳久、石毛 久美子
    • Total Pages
      487
    • Publisher
      創風社
    • ISBN
      9784883522385
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 神経変性疾患治療薬2016

    • Inventor(s)
      小菅康弘、石毛久美子、伊藤芳久
    • Industrial Property Rights Holder
      小菅康弘、石毛久美子、伊藤芳久
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-016245
    • Filing Date
      2016-01-29
    • Related Report
      2015 Research-status Report

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

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