Identifying the genes responsible for individual differences in increased vascular permeability during sepsis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18320
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kyoto University
• Principal Investigator: Seo Hideya 京都大学, 医学研究科, 助教 (40782652)
• Project Period (FY): 2020-03-01 – 2024-03-31
• Keywords: ICU-AW / β遮断薬 / 敗血症 / 血管透過性

Outline of Final Research Achievements

Due to the instability of the experimental system, the initial plan was modified, and the research focus was changed from vascular permeability caused by sepsis to ICU-acquired weakness (ICU-AW) caused by sepsis. With a focus on the activation of the muscle-specific Ubiquitin-Proteasome System (UPS), a primary pathology in ICU-AW, we identified genes that could be responsible for individual differences by comparing the expression of genes between UPS low-activation and high-activation groups. Furthermore, through pathway analysis, we narrowed down the pathological factors influencing disease progression, while simultaneously obtaining valuable data that could contribute to the development of preventive and therapeutic measures by elucidating mechanisms exacerbating prognosis. This study successfully demonstrates the concept that identification of causal mechanisms is feasible through exploring individual differences during sepsis.

Free Research Field

集中治療

Academic Significance and Societal Importance of the Research Achievements

ICU-AWの病態の詳細は未だ不明であり、効果的な治療や予防法がないことから、現代の集中治療が解決すべき大きな課題であった。本研究はICU-AW研究を加速させうる基礎データを提供することに成功した。
また、これまでの研究は個体によるばらつきが少なくなる条件に限定して実験を行っていた。この”ばらつき”にこそ病態を解明するうえでの重要な情報が隠されており、病勢の個体差利用した本研究では病態野探索のみならず、臨床的に介入可能な予防法、治療法を提示できることを示した。本研究手法は停滞する敗血症研究にとってブレイクスルーとなるであろう。