| Project/Area Number |
17K10152
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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(非常勤) (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), 准教授 (20276306)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 腎発生 / 母体低栄養 / エピジェネティクス / DNAヒドロキシメチル化 / 酸化ストレス / Tet / Sod3 / マイクロアレイ / 母体手栄養 / ヒドロキシメチル化 / 発生・分化 / 生理学 |
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| Outline of Final Research Achievements |
Global DNA hydroxymethylation and the expression of Tet proteins (Tet1, Tet2, Tet3) of metanephroi of offspring from nutrient-restricted rat dams (NR) were increased compared with control metanephroi. In organ culture, metanephroi exposed to ascorbic acid that facilitates Tet enzyme activity had significantly decreased ureteric bud tip number compared with controls. Dimethyloxallyl glycine, a small-molecule inhibitor of Tet, significantly decreased both ureteric bud branching and kidney size. We further identified Sod3 as a gene, whose hydroxymethylation was increased in NR. mRNA expression of Sod3 was decreased in NR. Sod3 is known to prevent the progression of chronic kidney disease and to protect mesenchymal stem cells from various stresses including nutrient deficiency and oxidative stress. Sod3 may play a role in low nephron number as well as aggravated tubular necrosis and fibrosis after unilateral ureteral obstruction in NR, which we previously reported.
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| Academic Significance and Societal Importance of the Research Achievements |
母体低栄養モデルラットにおけるネフロン数減少、および生後の二次侵襲による尿細管壊死、間質線維化の原因としてエピジェネティクス機構の関与が明らかになった。これにより現在問題となっている低出生体重児の増加、その結果としての慢性腎臓病を含む生活習慣病増加に対する予防、治療への対策の可能性が開かれた。
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