| Project/Area Number |
19K09014
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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 54040:Metabolism and endocrinology-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
HOSODA HIROSHI 国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (40359807)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ナトリウム利尿ペプチド / 腫瘍循環器学 / DNAメチル化 / 血管内分泌学 |
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| Outline of Research at the Start |
抗がん剤投与マウスの心筋組織を用いて、抗がん剤誘導性DNA損傷におけるANP・BNP遺伝子のプロモーター領域とエピジェネティック修飾の変化と意義、特にDNAメチル化及びDNMTとの機能的物理的な相互作用を明らかにするとともに、DNA損傷応答におけるDNAメチル化の役割について検討する。
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| Outline of Final Research Achievements |
Anticancer drug-induced heart failure impacts the quality of life and life expectancy of cancer patients, and remains a clinical and societal issue, but the mechanisms of cardiomyocyte injury remains unclear. In the present study, focusing on the transcriptional regulation of the BNP gene, the DNA damage response of cardiomyocytes induced by anticancer drugs and the role of epigenetic modifications in gene expression changes were investigated. The following were revealed: 1) Anticancer drug treatment resulted in cardiomyocyte DNA damage and suppression of ventricular BNP gene expression; 2) The suppression of BNP gene expression was accompanied by increased DNA methylation of the promoter region; 3) In mice deficient in cardiomyocyte-specific DNA methyltransferase, BNP gene suppression by anticancer drugs was not observed. During DNA damage in cardiomyocytes caused by anticancer drugs, the BNP gene expression is regulated by the DNA methylation modification system.
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| Academic Significance and Societal Importance of the Research Achievements |
果によって、抗がん剤心毒性の病態理解や心筋細胞のDNA損傷応答の解明、心不全バイオマーカー応用研究等への展開が期待できる。
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