• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The kinetics of autophagy following septic insults from metabolomics analyses - Exploration of novel biomarkers on sepsis -

Research Project

Project/Area Number 18H02901
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionChiba University

Principal Investigator

Watanabe Eizo  千葉大学, 大学院医学研究院, 特任教授 (40375639)

Co-Investigator(Kenkyū-buntansha) 幡野 雅彦  千葉大学, 大学院医学研究院, 教授 (20208523)
伊藤 千鶴  千葉大学, 大学院医学研究院, 講師 (80347054)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords敗血症 / メタボロミクス / バイオマーカー / オートファジー / 細胞死 / タンパク構成アミノ酸 / 細菌性腹膜炎 / 酸化ストレス / メタボローム解析 / 盲腸結紮穿孔 / 腹膜炎
Outline of Final Research Achievements

We sought to investigate the detailed mechanism of autophagy regulation in sepsis. Moreover, we wanted to clarify the characteristics of plasma metabolites in septic patients due to perforation of the digestive tract and the mouse model of sepsis, i.e., cecal ligation and punctures (CLP) by metabolomic analysis using the plasma. As results, proteinogenic amino acids, Ceramide, Gly/Ser/Thr were common pathways between septic patients and mice due to peritonitis. On the other hand, when we compare metabolites of CLP liver from Alb-CreERT2/Atg5f/f (KO) mice and those of wild-type mice (WT), 97 and 49 metabolites were extracted at 8 hrs and 24 hrs after CLP surgery, respectively. Among them, the four metabolites are related to oxidative stress. Furthermore, the five metabolites segregated the KO CLP from WT CLP in the liver, of which electron transfer system, glucose metabolism, and dipeptide-associated metabolites were listed.

Academic Significance and Societal Importance of the Research Achievements

敗血症は,感染症の最重症病態であるが,その病態自体に対する治療薬は未開発である.一方,敗血症モデルマウスにおいて,敗血症急性期ではオートファジーが一過性に亢進し,その後抑制傾向となること,そしてそのことが炎症反応や転帰に悪影響を及ぼしていることが判明していた.本研究では,メタボロミクスで発見されたオートファジー誘導物質の投与により,オートファジー調節を介した敗血症治療に結びつけることが最終目的である.今回,ヒトとマウスで同様の敗血症(腹膜炎)の検体を用い,血漿によるメタボロミクスを比較,共通代謝経路を導出できたことから,今後のオートファジー経路からの敗血症バイオマーカー検索に繋がった.

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (3 results)

All 2021 2019

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

  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)12021

    • Author(s)
      Daniel J Klionsky、Shu Aizawa、Amal Kamal Abdel-Aziz、Sara Abdelfatah、Mahmoud Abdellatif、Asghar Abdoli、Steffen Abel、Hagai Abeliovich、Marie H Abildgaard、Yakubu Princely Abudu、Abraham Acevedo-Arozena、Iannis E Adamopoulos、Khosrow Adeli、Timon E Adolph、Annagrazia Adornetto、Elma Aflaki、Galila Agam et al.
    • Journal Title

      Autophagy

      Volume: 17 Issue: 1 Pages: 1-382

    • DOI

      10.1080/15548627.2020.1797280

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 敗血症時のAutophagyと栄養管理2019

    • Author(s)
      渡邉 栄三
    • Journal Title

      外科と代謝・栄養

      Volume: 53 Pages: 287-292

    • NAID

      130007784964

    • Related Report
      2018 Annual Research Report
  • [Presentation] 敗血症病態におけるMitophagyの役割とその制御の可能性2021

    • Author(s)
      渡邉栄三,林 洋輔,大網毅彦,藤村理紗,幡野雅彦
    • Organizer
      日本外科代謝栄養学会第58回学術集会
    • Related Report
      2020 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi