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Differential roles of RAGE species for renal tubular damages

Research Project

Project/Area Number 19K23941
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionKanazawa University

Principal Investigator

Miyagawa Taro  金沢大学, 附属病院, 特任助教 (20738207)

Project Period (FY) 2019-08-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords急性腎障害 / RAGE / sRAGE / HMGB1 / 尿細管障害
Outline of Research at the Start

終末糖化産物の特異受容体receptor for advanced glycation end products(RAGE)は、様々な疾患の進展やその抑制に関与している。
申請者らは腎臓病患者でHigh mobility group box 1(HMGB1)、RAGEが糸球体・間質病変の進展機序に関与することを示した。この結果から尿細管障害の進展機序にRAGEを介したシグナル伝達が関与すると仮説を立てた。尿細管障害モデルマウスや培養尿細管細胞における、RAGEシグナルの動態や機能・遺伝子解析を検討する。
本研究から腎臓病が腎不全へ至る機序が明らかとなり、進展抑制に関する知見を得ることが可能となる。

Outline of Final Research Achievements

Acute kidney injury (AKI) is an important risk factor for the development of chronic kidney disease and end-stage renal failure. This study focused on soluble RAGE (sRAGE) and investigated the protective mechanism of sRAGE against AKI. In an ischemia-reperfusion model of AKI, RAGE deficiency exacerbated AKI.
In proximal tubular cells exposed to hypoxia, inflammatory cytokines including high mobility group box 1 (HMGB1) were decreased and cell proliferative capacity was improved in the presence of sRAGE.
In an AKI model, sRAGE treatment reduced AKI. These results suggest that sRAGE may be protective in ischemia-reperfusion-induced AKI.

Academic Significance and Societal Importance of the Research Achievements

虚血再灌流による尿細管障害を背景としたAKIにおいて、デコイ型受容体であるsRAGEの存在が重要な機能を担い、HMGB1がsRAGEに捕捉され、腎障害が軽減する可能性があることが初めて明らかとなった。さらに、リコンビナントsRAGEの投与により、HMGB1の炎症性シグナルが抑制され、腎障害に対し保護的に働くことも分かった。以上より、RAGE/sRAGEを介したAKI発症の分子機序が明らかになるとともに、sRAGE補充療法がAKIの新規治療法として有用である可能性が示された。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2022 2020 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury2022

    • Author(s)
      Miyagawa Taro、Iwata Yasunori、Oshima Megumi、Ogura Hisayuki、Sato Koichi、Nakagawa Shiori、Yamamura Yuta、Kamikawa Yasutaka、Miyake Taito、Kitajima Shinji、Toyama Tadashi、Hara Akinori、Sakai Norihiko、Shimizu Miho、Furuichi Kengo、Munesue Seiichi、Yamamoto Yasuhiko、Kaneko Shuichi、Wada Takashi
    • Journal Title

      Biology Open

      Volume: 11 Issue: 1 Pages: 1-8

    • DOI

      10.1242/bio.058852

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Differential roles of RAGE species for renal tubular damages2020

    • Author(s)
      Taro Miyagawa
    • Organizer
      18th Asian Pacific Congress of Nephrology 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 尿細管障害における RAGE分子種の機能的役割2019

    • Author(s)
      宮川 太郎
    • Organizer
      第9回西日本腎臓病研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 尿細管障害における RAGE分子種の機能的役割2019

    • Author(s)
      宮川 太郎
    • Organizer
      第40回炎症・再生医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Differential roles of RAGE species for renal tubular damages2019

    • Author(s)
      Taro Miyagawa
    • Organizer
      ASN Kidney Week 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] 尿細管障害における RAGE分子種の機能的役割2019

    • Author(s)
      宮川 太郎
    • Organizer
      第23回日本心血管内分泌代謝学会学術総会
    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2023-01-30  

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