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Study of the pathophysiological significance of endogenous AGE as an exacerbating factor for tissue remodeling, and the development of novel targeted therapy

Research Project

Project/Area Number 18K06807
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionShujitsu University

Principal Investigator

MORI Shuji  就実大学, 薬学部, 教授 (50220009)

Co-Investigator(Kenkyū-buntansha) 豊村 隆男  就実大学, 薬学部, 講師 (40425137)
渡邊 政博  就実大学, 薬学部, 講師 (10758246)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords炎症 / 組織リモデリング / サイトカイン / 医療薬学
Outline of Final Research Achievements

We investigated the identification of novel binding factors for Damps or AGEs molecules with the pattern recognition receptors-stimulating activity, the formation of inflammatory complex and their pathophysiological significance. The chromatographic analysis using AGEs-immobilized affinity gel revealed the existence of some binding factors. Recombinant binding factor was shown to affect the damps-induced inflammatory response in macrophage cells. This finding suggests that there is the control mechanism by the complex formation with damps, suggesting the further understanding of tissue remodeling associated with chronic inflammation and its applicability as new drug discovery target.

Academic Significance and Societal Importance of the Research Achievements

生活習慣病の増悪化因子としてDampsやAGEs分子による過剰な免疫応答に焦点をあて,それらの生体内活性制御機構の解析研究を実施した。特に,結合因子の同定,起炎性複合体の形成に着目して研究を進めたところ,複数個の結合因子の存在が明らかとなり,これらの結合因子はDamps刺激による炎症応答に対して有意に影響を与えることが明らかとなった。本知見は,Damps複合体形成に伴う炎症応答制御機構の存在の可能性を拓くとともに,組織リモデリング病態の分子理解と新たな治療標的としての応用性を示唆するものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Advanced glycation end products (AGEs) synergistically potentiated the proinflammatory action of lipopolysaccharide (LPS) and high mobility group box-1 (HMGB1) through their direct interactions.2020

    • Author(s)
      Watanabe M, Toyomura T, Tomiyama M, Wake H, Liu K, Teshigawara K, Takahashi H, Nishibori M, Mori S.
    • Journal Title

      Mol Biol Rep.

      Volume: 47(9) Issue: 9 Pages: 7153-7159

    • DOI

      10.1007/s11033-020-05783-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential contribution of possible pattern‐recognition receptors to advanced glycation end product?induced cellular responses in macrophage‐like RAW264.7 cells2019

    • Author(s)
      Watanabe Masahiro、Toyomura Takao、Wake Hidenori、Liu Keyue、Teshigawara Kiyoshi、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Biotechnology and Applied Biochemistry

      Volume: in press Issue: 2 Pages: 265-272

    • DOI

      10.1002/bab.1843

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The C‐terminal region of tumor necrosis factor like weak inducer of apoptosis is required for interaction with advanced glycation end products2018

    • Author(s)
      Watanabe Masahiro、Toyomura Takao、Wake Hidenori、Liu Keyue、Teshigawara Kiyoshi、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Biotechnology and Applied Biochemistry

      Volume: 66 Issue: 2 Pages: 254-260

    • DOI

      10.1002/bab.1706

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] AGEs結合因子の探索と結合遮断ペプチドの同定2020

    • Author(s)
      森 秀治 他
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] AGEs結合因子の単離とAGEs-RAGE結合抑制領域の同定2020

    • Author(s)
      森 秀治 他
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] AGEs結合因子としてのLfの同定とマクロファージTNF-α発現応答変化2019

    • Author(s)
      森秀治 他
    • Organizer
      第40回日本炎症・再生医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] AGEsとDAMPsの協調作用の検討2019

    • Author(s)
      渡邊政博 他
    • Organizer
      第58回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] AGEs結合因子の分子同定と炎症性サイトカイン発現応答への影響2019

    • Author(s)
      森秀治 他
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pathophysiological role of a factor affecting AGEs-RAGE interaction on endothelial cell responses2018

    • Author(s)
      Mori S et al
    • Organizer
      第18回国際薬理学・臨床薬理学会議
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] TWEAK誘導性内皮細胞応答と終末糖化産物による抑制2018

    • Author(s)
      森 秀治 他
    • Organizer
      第39回日本炎症・再生医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 遺伝子改変細胞を用いたDAMPs分子の作用メカニズム解析2018

    • Author(s)
      渡邊政博 他
    • Organizer
      第133回日本薬理学会近畿部会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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