2023 Fiscal Year Final Research Report

Profiling of circulating micro RNA expression in patients with sepsis

Research Project

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Project/Area Number	20K09305
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55060:Emergency medicine-related
Research Institution	Osaka University
Principal Investigator	Umemura Yutaka 大阪大学, 大学院医学系研究科, 招へい教員 (20743561)
Co-Investigator(Kenkyū-buntansha)	嶋津岳士大阪大学, 大学院医学系研究科, 教授 (50196474) 山川一馬大阪医科薬科大学, 医学部, 准教授 (50597507) 小倉裕司大阪大学, 大学院医学系研究科, 准教授 (70301265) 藤見聡地方独立行政法人大阪府立病院機構大阪急性期・総合医療センター(臨床研究支援センター), 救急診療科, 主任部長 (70362720) 松本寿健大阪大学, 医学部附属病院, 特任助教(常勤) (70644003)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	敗血症 / 全身炎症反応 / 臓器障害 / 自然免疫 / マイクロRNA
Outline of Final Research Achievements	In the first phase of the study, mRNA and miRNA contained in peripheral blood leukocytes were extracted from 30 patients with sepsis and 10 healthy controls, and the expression patterns of mRNA and miRNA were analyzed using a next-generation sequencer, and compared between healthy subjects and sepsis. As a result, the expression of miRNA and mRNA in sepsis leukocytes was significantly correlated and several patterns were inversely correlated. In the second phase of the study, 12 patients and 4 healthy controls were subjected to RNA sequencing of plasma miRNA (circulating miRNA) in addition to leukocyte mRNA and miRNA, and differentially expressed genes were analyzed compared to sepsis patients and healthy controls. Among leukocyte mRNA, genes involved in the Th2 signaling pathway, such as GATA3, were the most repressed. In circulating miRNA, increased expression of 12 RNAs associated with GATA3 mRNA was observed.
Free Research Field	救急医学
Academic Significance and Societal Importance of the Research Achievements	本研究結果は敗血症患者における炎症・臓器障害を進行させる重要なメカニズムの一つとして、miRNAによるmRNA発現の制御が関与している可能性を示唆するものであった。また同じ経路を制御するためのmiRNAでも白血球と循環中のRNAで発現が大きく異なることが示され、炎症における細胞間の情報伝達の全容解明に大きく寄与する結果と考えられる。今後は信頼性の高い次世代マーカーとしての精度や簡易的な測定基盤を整えるための研究推進が必要であり、本研究はその基盤となるものである。