Lipidomic analyses of circulating exosomes for biomarker discovery in drug-induced liver injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16365
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Sun Yuchen 国立医薬品食品衛生研究所, 医薬安全科学部, 研究員 (60818904)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エキソソーム / リピドミクス / 薬物性肝障害 / バイオマーカー

Outline of Final Research Achievements

In this study, we aimed to identify a novel biomarker that enables early detection of drug-induced liver injury (DILI). To this end, we performed phospholipidomic analysis using plasma exosomes obtained from an animal model for DILI which was made by repeated administration of carbon tetrachloride. As a result of the analysis, it was found that the abundance of several types of exosomal lipids including the lysophosphatidylcholine species were significantly reduced upon the occurrence of liver injury. In addition, it was also found that these exosomal lipid molecules had high diagnostic potentials for the detection of early liver injury in which a conventional biomarker ALT does not respond.

Free Research Field

薬物動態学、分析化学

Academic Significance and Societal Importance of the Research Achievements

本研究は肝障害の発生時に分泌されるエキソソームのリピドームを網羅的に解析することにより、その早期発見に有用なExo-lipidsバイオマーカー分子を複数種同定することができた。本研究で同定されたバイオマーカー分子は新規医薬品の非臨床安全性試験等における肝障害の発生の検出に利用できると考えられる。加えて、本研究ではリキッドバイオプシー分野で特に注目されているエキソソームとDILIとの関連をリピドームという切り口で解析した世界初の研究であり、本研究成果により今後肝障害時におけるエキソソーム脂質の病態生理学的意義の解明につながることが期待される。