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Analysis of protective mechanism of acute lung injury via serotonin transporter/serotonin blockade

Research Project

Project/Area Number 16K09544
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNagasaki University

Principal Investigator

TANAKA Takeshi  長崎大学, 病院(医学系), 講師 (30432967)

Co-Investigator(Kenkyū-buntansha) 森本 浩之輔  長崎大学, 熱帯医学研究所, 准教授 (50346970)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsセロトニン / 血管透過性亢進 / 敗血症性ショック / ARDS / ROCK / Rhoキナーゼ / 急性肺障害 / 敗血症
Outline of Final Research Achievements

5-HIAA levels were significantly higher in septic shock patients than in patients without shock or healthy controls . These elevated levels were correlated with severity indexes (SOFA , APACHE-II , and PaO2:FiO2 ), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration and ICU duration ). In vitro experiment, serotonin increased the permeability of endothelial cells (ECs); its increase was inhibited by ROCK inhibitor.And also elevated levels of 5HIAA were seen in ARDS with septic shock patients(higher level than in ARDS without septic shock patients).
These suggest a novel mechanism that serotonin would disrupt endothelium barriers via RhoA/ROCK signal and cause the pathogenesis of ARDS and septic shock with a vascular leak. Serotonin could be a novel vascular permeability biomarker.

Academic Significance and Societal Importance of the Research Achievements

ARDSや敗血症性ショックの病態主因である血管透過性亢進を制御する治療法の開発が難しい中で、その機序へ直接作用し得るセロトニン拮抗とROCK活性へのアプローチで知見を解析した研究であり、将来の治療薬開発につながるアプローチと考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018 2017

All Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Serotonin and vascular permeability (Serotonin beyond the brain) --- Analysis of Serotonin in Sepsis and ARDS2018

    • Author(s)
      田中 健之
    • Organizer
      23rd Congress of Asian Pacific Society of Respirology (APSR 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] セロトニンと血管透過性亢進(Serotonin beyond the brain)― 敗血症、ARDSでの解析(中間解析)2017

    • Author(s)
      田中 健之
    • Organizer
      第53回肺サーファクタント関連医学会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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