Exosomal Nucleic Acids Reflecting Hematopoietic Progenitor Cell Dysfunction Remaining Long-Term after Oxidative Injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Hirabayashi Yoko 国立医薬品食品衛生研究所, 安全性生物試験研究センター, センター長 (30291115)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: エクソソームRNA / 造血幹・前駆細胞 / γ線照射

Outline of Final Research Achievements

This study was planned to elucidate the molecular basis of the failure of recovery that remains almost throughout life, especially in the hematopoietic stem/progenitor cell fraction, which is considered to be the pathogenic mechanism of prolonged disorders, including leukemia, induced after recovery from γ-irradiation received at a young age. Here, we analyzed small RNAs in exosomes isolated from bone marrow cells of aged mice irradiated with γ-rays at a young age and non-irradiated mice equivalent in age, and identified those that were clearly down-regulated in the irradiated group compared to the non-irradiated group. Furthermore, since many of the predicted target genes included so-called oncogenes, the results suggest that irradiation disrupts the repression of these target genes and activates them, contributing to carcinogenesis and subsequent proliferation.

Free Research Field

基礎医学

Academic Significance and Societal Importance of the Research Achievements

エクソソームRNAは、がん診断のバイオマーカーのみならず、炎症のマーカーとしての有用性なども示唆されている。末梢血からも分離可能であり、本研究結果においては具体的なマーカー遺伝子の提言には至らなかったが、今後、研究成果を踏まえ分子機序に根ざした有用なマーカー遺伝子を同定することで、長期にわたり遷延する異常を定期的な血液検査によってモニター可能となることが期待される