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Development of early diagnosis for sepsis focused on histone hold in extracellular vesicles

Research Project

Project/Area Number 18K08425
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionNational Center for Geriatrics and Gerontology (2022)
Nippon Medical School (2018-2020)

Principal Investigator

Soda Keita  国立研究開発法人国立長寿医療研究センター, 研究所 ジェロサイエンス研究センター, 研究員 (80794502)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords血管内皮細胞 / 細胞傷害 / 細胞外ヒストン / 細胞外ベジクル / ヒストン / 敗血症 / 血管内皮細胞傷害
Outline of Final Research Achievements

Extracellular histones have been shown to induce endotoxicity to the vascular endothelial cells in severe inflammation such as sepsis. In this study, we found that extracellular vesicles (EVs) were released from human umbilical vein endothelial cells after histone addition. Since TNFα is known to release EVs from endothelial cells during inflammation, we compared the membrane protein of TNFα-derived and histone-derived EVs by proteomics analysis. We showed that the identified membrane proteins were useful markers for the evaluation of histone-induced endothelial injury. We also showed that EVs were formed around the plasma membrane by the electron microscopy, and histone aggregates on the plasma membrane by the immunoelectron microscopy. In addition, this EVs propagates the cytotoxicity to other endothelial cells.

Academic Significance and Societal Importance of the Research Achievements

好中球細胞外トラップ(NETs)やNETs由来の細胞外ヒストンによる血管内皮細胞の傷害は、敗血症などの重傷炎症からCOVID-19に至るまで多様な疾患の病因に関与している。しかしながら、血管内皮細胞傷害の予測に血中ヒストンを対象とした報告は限られる。我々の結果はヒストンによる細胞機能障害の標的を明らかにし、細胞外ベジクル上のヒストンと膜タンパク質のフローサイトメトリーによる検出が、ヒストンによる内皮傷害の評価に有用なマーカーとなることを示唆するものである。血中ヒストンを内皮細胞傷害の予測因子として診断に応用できれば敗血症などの重症炎症の予防及び判定に有用であり医学的・社会的意義は高い。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Presentation (1 results)

  • [Presentation] 血管内皮細胞傷害により生じるベジクルの膜タンパク質プロテオミクス2019

    • Author(s)
      早田敬太
    • Organizer
      第15回日本臨床プロテオゲノミクス研究会
    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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