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Identification of inflammation suppressive DAMPs and their pathophysiological significance in inflammatory diseases

Research Project

Project/Area Number 21K06701
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

WATANABE Masahiro  就実大学, 薬学部, 准教授 (10758246)

Co-Investigator(Kenkyū-buntansha) 豊村 隆男  就実大学, 薬学部, 准教授 (40425137)
森 秀治  就実大学, 薬学部, 教授 (50220009)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsダメージ関連分子パターン / DAMPs / HMGB1 / LPS / リボソームタンパク質 / 終末糖化産物 / AGEs / 炎症 / 相互作用
Outline of Research at the Start

これまでの検討により,我々が見出した終末糖化産物(AGEs)と結合する新規分子(AGE-BP)は,AGEsと同様に生体内で炎症を引き起こすダメージ関連分子パターン(DAMPs)と類似した挙動を示すことが明らかになった.さらに,AGE-BPは,DAMPsが炎症を誘導する作用を抑制することが示唆された.これらの知見は,AGE-BPは,DAMPsの作用を制御する炎症抑制性DAMPsである可能性を示していると考えた.そこで本研究では,AGE-BP が新たな概念である炎症抑制性DAMPs であることを実証し,炎症により生じる疾患における既知のDAMPs やAGEs との関係を解明することを目指す.

Outline of Final Research Achievements

Recently, it has been revealed that biomolecules (damage-associated molecular patterns: DAMPs) that have migrated to different locations from their original sites in the body due to various factors induce inflammation. DAMPs may cause diseases such as diabetes, age-related changes in physiological functions, and cancer, which are believed to be caused by lifestyle-related factors. In this study, we demonstrated the existence of molecules that appear by a mechanism similar to that of DAMPs and inhibit the action of DAMPs (suppressive DAMPs).

Academic Significance and Societal Importance of the Research Achievements

DAMPsが種々の慢性炎症が原因となる疾患の要因となる可能性は既に指摘され,DAMPsを標的とした新規疾患治療法が模索されている.本研究では,生体内にDAMPsと対になって炎症を制御するメカニズム(抑制性DAMPs)が存在する可能性を示した.抑制性DAMPsの発見は,DAMPsによる炎症反応を制御するメカニズムに新たな知見を追加することのみならず,DAMPsを標的とした治療法を考える上で,新たな標的となる可能性を有しており,今後の新規治療法の開発や創薬に寄与することが期待できる.

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Glycolaldehyde-derived advanced glycation end products promote macrophage proliferation via the JAK-STAT signaling pathway2023

    • Author(s)
      Toyomura Takao、Watanabe Masahiro、Wake Hidenori、Nishinaka Takashi、Hatipoglu Omer Faruk、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Molecular Biology Reports

      Volume: 50 Issue: 7 Pages: 5849-5858

    • DOI

      10.1007/s11033-023-08509-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cationic ribosomal proteins can inhibit pro‐inflammatory action stimulated by LPS+HMGB1 and are hindered by advanced glycation end products2023

    • Author(s)
      Watanabe Masahiro、Toyomura Takao、Wake Hidenori、Nishinaka Takashi、Hatipoglu Omer Faruk、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Biotechnology and Applied Biochemistry

      Volume: 71 Issue: 2 Pages: 264-271

    • DOI

      10.1002/bab.2538

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nordihydroguaiaretic acid inhibits glyoxalase I, and causes the accumulation of methylglyoxal followed by cell-growth inhibition2022

    • Author(s)
      Watanabe Masahiro、Toyomura Takao、Ikegami Ryo、Suwaki Yui、Sada Minami、Wake Hidenori、Nishinaka Takashi、Hatipoglu Omer Faruk、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Molecular Biology Reports

      Volume: 49 Issue: 11 Pages: 10499-10507

    • DOI

      10.1007/s11033-022-07929-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of ribosomal protein L9 as a novel regulator of proinflammatory damage-associated molecular pattern molecules2022

    • Author(s)
      Watanabe Masahiro、Toyomura Takao、Wake Hidenori、Nishinaka Takashi、Hatipoglu Omer Faruk、Takahashi Hideo、Nishibori Masahiro、Mori Shuji
    • Journal Title

      Molecular Biology Reports

      Volume: 49 Issue: 4 Pages: 2831-2838

    • DOI

      10.1007/s11033-021-07096-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 抑制性DAMPsとしてのリボソーム構成分子RPL9の同定2022

    • Author(s)
      渡邊政博,豊村隆男,和氣秀徳,西中崇,ハティポール オメル ファルク,高橋英夫,西堀正洋,森 秀治
    • Organizer
      第141回日本薬理学会近畿部会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新規AGEs結合分子AGE-BP2がDAMPsの作用に与える影響の解析2021

    • Author(s)
      渡邊政博,豊村隆男,和氣秀徳,西中崇,逢坂大樹,王登莉,高橋英夫,西堀正洋,森 秀治
    • Organizer
      第139回日本薬理学会近畿部会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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