Pathophysiology of Post-Traumatic Lung Injury through Single-Cell Analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16585
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Senda Atsushi 東京医科歯科大学, 東京医科歯科大学病院, 助教 (00728040)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 外傷出血性モデル / 虚血再還流 / 多臓器不全

Outline of Final Research Achievements

Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are involved in the development of systemic inflammation. Our study elucidated the multiple changes that simultaneously occur in exosomes after ischemic stimulation. We found that lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activate inflammation, including the NF-κB pathway. Based on the above, we are currently gathering data on the relation between each cell component and the provoked inflammation utilizing the techniques of single-cell analysis.

Free Research Field

外傷

Academic Significance and Societal Importance of the Research Achievements

我々の研究成果は腸管虚血が全身性の炎症をきたす病態の解明に寄与をしました。脂質解析、タンパク定量、mRNAについて包括的な解析を行い、提示することにより本病態に関与するあらゆる仮説に対して有益な基礎的な情報を提示しました。また、代謝ネットワークに関するin sillicoな解析を行うことにより、上記で得られたデータの持つ意義について提示を行いました。以上のように個体レベルで起きる変化について得られた情報をより詳細に解析するため細胞レベルでの変化を調べるための実験系を確立し、今後より詳細な病態解明に繋げる手法を開発しました。