| Project/Area Number |
18K14909
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Kyoto Pharmaceutical University (2020)
Suzuka University of Medical Science (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 好中球細胞外トラップ / NETs / NETosis / エピジェネティクス / DNAメチル化 / PAD4 / ヒストンシトルリン化 |
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| Outline of Final Research Achievements |
We investigated the role of epigenetics, especially DNA methylation to elucidate the mechanisms of NETosis, cell death of neutrophil. In this study, NETosis in the neutrophil-like cells was induced by the treatment with 5-azacytidine (Aza), DNMT1 inhibitor. Moreover, Aza increased PAD4 expression, and PAD4 inhibition and mitochondrial reactive oxygen species scavenger tended to decrease Aza-induced NETosis.
Overall, our results suggested that NETosis induction was regulated by changes in DNA methylation status.
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| Academic Significance and Societal Importance of the Research Achievements |
NETosis誘導におけるPAD4の発現や活性酸素の関与は知られている。しかし、様々な疾患におけるエピジェネティック異常の観点からNETosisの誘導機構を指摘した報告は全くない。本研究では、好中球の分化過程におけるDNAメチル化制御の観点からNETosis誘導機構の一端を明らかにした。
本研究における好中球のDNAメチル化状態とそれに起因するNETosisの誘導機構の知見は、NETosisが誘導される様々な疾患の病態悪化機構の解明に向けた重要な情報を提供できたと考える。
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