Prevention of low nephron number by modulation of DNA methylation
| Project/Area Number |
26461620
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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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| Research Field |
Pediatrics
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| Research Institution | Keio University |
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Principal Investigator |
Awazu Midori 慶應義塾大学, 医学部(信濃町), 講師 (20129315)
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| Co-Investigator(Kenkyū-buntansha) |
飛彈 麻里子 慶應義塾大学, 医学部(信濃町), 共同研究員 (20276306)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 小児腎・泌尿器学 / ネフロン数 / DNAメチレーション / エピジェネティクス / 母体低栄養 / 尿管芽分岐 / DNAメチルトランスフェラーゼ / 器官培養 / DNAメチル化 / 葉酸 / DNAヒドロキシメチル化 / 後腎 / DNMT1 / 小児腎臓学 / プログラミング / DNAメチル化酵素 / シグナル伝達 |
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| Outline of Final Research Achievements |
In metanephroi from embryos of nutrient restricted rat dams, global DNA methylation is reduced, and the reduction in DNA methyltransferase 1, an enzyme that maintains DNA cytosine methylation, was thought to be the cause. DNA methylation inhibitor 5-Aza-2′-deoxycytidine inhibited ureteric branching and metanephros growth in organ culture. On the other hand, folic acid supplementation to nutrient restricted mothers improved the reduction in ureteric branching, kidney size, glomerular density, and DNA methylation in the fetal kidney. Medium deficient in methyl donors including folic acid decreased ureteric branching and metanephros growth in organ culture, whereas the addition of folic acid to the medium improved the phenotype of metanephroi of fetuses from nutrient restricted mothers. Thus DNA methylation is necessary for kidney development and maternal folic acid supplementation may prevent low nephron number due to maternal nutrient restriction.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Renal complications in 6p duplication syndrome: microarray-based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS).2015
Author(s)
Yoshimura-Furuhata M, Nishimura-Tadaki A, Amano Y, Ehara T, Hamasaki Y, Muramatsu M, Shishido S, Aikawa A, Hamada R, Ishikura K, Hataya H, Hidaka Y, Noda S, Koike K, Wakui K, Fukushima Y, Matsumoto N, Awazu M, Miyake N, Kosho T.
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Journal Title
Am J Med Genet A
Volume: 167
Issue: 3
Pages: 592-601
DOI
Related Report
Peer Reviewed / Open Access
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