| Project/Area Number |
18K07053
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | National Institute of Health Sciences |
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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)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | エクソソームRNA / 造血幹・前駆細胞 / γ線照射 / 造血幹細胞 / エクソソーム / 造血ニッチ / 造血幹前駆細胞 / 電離放射線 / 化学物質 / 酸化ストレス |
|---|
| 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.
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| 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
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