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Cytotoxicity of chromatin from macrophages in rhabdomyolysis-induced acute kidney injury

Research Project

Project/Area Number 16K19497
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionKeio University

Principal Investigator

Okubo Koshu  慶應義塾大学, 医学部(信濃町), 共同研究員 (60749125)

Research Collaborator KUROSAWA Miho  
URANO Yasuteru  
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords横紋筋融解症 / 急性腎障害 / 白血球細胞外トラップ / Mac-1
Outline of Final Research Achievements

Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation. The muscle damage can lead to acute kidney injury (AKI).Recently, macrophages were implicated in the disease pathogenesis of rhabdomyolysis-induced AKI, but the precise molecular mechanism remains unclear. In the present study, we show that macrophages released extracellular traps (ETs) comprising DNA fibers and granule proteins in a mouse model of rhabdomyolysis. Heme-activated platelets released from necrotic muscle cells during rhabdomyolysis enhanced the production of macrophage extracellular traps (METs). Here we report, this unanticipated role for METs and platelets as a sensor of myoglobin-derived heme in rhabdomyolysis-induced AKI. Also, we found a new therapeutic tool for prevention of AKI after rhabdomyolysis, which might rescue some sufferers of this pathology.

Report

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

    (4 results)

All 2018 2017 2016

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

  • [Journal Article] Macrophage extracellular chromatin release induced by Mac-1 mediated platelet-macrophage interactions triggers acute kidney injury in rhabdomyolysis.2018

    • Author(s)
      Okubo K, Kurosawa M, Kamiya M, Urano Y, Suzuki A, Yamamoto K, Hase K, Homma K, Sasaki J, Miyauchi H, Hoshino T, Hayashi M, Mayadas TN, Hirahashi J.
    • Journal Title

      Nat. Med.

      Volume: 24 Issue: 2 Pages: 232-238

    • DOI

      10.1038/nm.4462

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Macrophage extracellular traps induced by Mac-1 (CD11b/CD18) dependent platelet-macrophage interactions progress acute kidney injury2017

    • Author(s)
      Koshu Okubo
    • Organizer
      The 18th International Vasculitis and ANCA Workshop
    • Place of Presentation
      伊藤国際学術研究センター (東京都文京区)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Macrophage Extracellular Traps Induced by Mac-1 (CD11b/CD18) Dependent Platelet-Macrophage Interactions Promotes Acute Kidney Injury in Rhabdomyolysis2016

    • Author(s)
      Koshu Okubo
    • Organizer
      ASN Kidney Week 2016 (American Society of Nephrology)
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 好中球細胞外トラップ形成における活性酸素認識プローブを用いた新規イメージング技術の応用2016

    • Author(s)
      大久保光修
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2019-03-29  

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