2023 Fiscal Year Final Research Report

Innovative approach to diagnosis of fatal hypothermia using cold-responsive miRNA expression profiles

Research Project

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Project/Area Number	21K19653
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 58:Society medicine, nursing, and related fields
Research Institution	University of Occupational and Environmental Health, Japan (2022-2023) Nagasaki University (2021)
Principal Investigator	Umehara Takahiro 産業医科大学, 医学部, 准教授 (60617421)
Co-Investigator(Kenkyū-buntansha)	村瀬壮彦長崎大学, 医歯薬学総合研究科(医学系), 助教 (40823315) 池松和哉長崎大学, 医歯薬学総合研究科(医学系), 教授 (80332857) 佐藤寛晃産業医科大学, 医学部, 教授 (50441845)
Project Period (FY)	2021-07-09 – 2024-03-31
Keywords	低体温 / 低酸素 / microRNA
Outline of Final Research Achievements	In this study, we investigated miRNA-mRNA molecular interactions using miRNA mimic or mRNA siRNA in primary cultured iliopsoas muscle cells. The expression of hypoxia-related genes, which are target genes of miR-203a showed a significant increase in extreme hypothermia. Molecular dynamic analysis using miRNA mimic revealed significantly decreasing expression of hypoxia-related genes with miR-203a overexpression. The hypoxia-related genes whose expression changes were observed are involved in apoptosis and angiogenesis. Accordingly, this study revealed that a biological defense mechanism via activation of the miR-203a-hypoxia-related genes axis works to prevent necrosis induced by extreme hypothermia. Furthermore, it was suggested that miR-203a and hypoxia-related genes may serve as novel molecular markers to complement the definitive diagnosis of fatal hypothermia.
Free Research Field	法医学
Academic Significance and Societal Importance of the Research Achievements	凍死の診断は、特異的な所見がなく主観的な所見に頼らざるを得ないため、科学的かつ客観的な確定診断法を確立することは法医実務にとって重要な課題である。本研究では、死後変化の影響を受けにくいmicroRNAを中心とした低体温の分子メカニズムの一端を解明できた。これらの成果は、法医学分野にとどまらない成果であり、それら遺伝子群を凍死特異的な新しい分子診断マーカーとして実務応用できる可能性が非常に高いものと考える。また、これらの成果の実務展開により、精度が高く、刑事裁判資料等の使用に耐えうる司法解剖鑑定書・行政解剖報告書を作成することで、研究成果を積極的に社会に還元することが可能となる。