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KAKEN_17K10152seika.pdf
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Title |
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DNAメチル化、ヒドロキシメチル化のラット正常腎、母体低栄養腎における役割の解明
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DNA メチルカ、ヒドロキシメチルカ ノ ラット セイジョウジン、ボタイ テイエイヨウジン ニ オケル ヤクワリ ノ カイメイ
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DNA mechiruka, hidorokishimechiruka no ratto seijōjin, botai teieiyōjin ni okeru yakuwari no kaimei
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DNA methylation and hydroxymethylation in the kidney from offspring of nutrient restricted rats
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粟津, 緑
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アワズ, ミドリ
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Awazu, Midori
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慶應義塾大学・医学部 (信濃町) ・講師 (非常勤)
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Research team head
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科研費研究者番号 : 20129315
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飛彈, 麻里子
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ヒダ, マリコ
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Hida, Mariko
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慶應義塾大学・医学部 (信濃町) ・准教授
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Research team member
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科研費研究者番号 : 20276306
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2020
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科学研究費補助金研究成果報告書
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2019
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母体低栄養ラット後腎における全般的DNAヒドロキシメチル化 (5hmC化) およびTet酵素 (Tet1、2、3) は増加していた。またTetを介し5hmC化を促進するビタミンCとTet阻害薬dimethyloxallyl glycineは共に尿管芽分岐を抑制した。さらに母体低栄養腎で5hmC化が増加している遺伝子としてSod3を同定した。Sod3のmRNA発現は母体低栄養で減少していた。Sod3は慢性腎臓病進展を防ぎ、種々のストレスから間葉系幹細胞を保護することが報告されている。母体低栄養によるネフロン数減少、成獣における腎線維化増悪の機序としてSod3の5hmC化が関与している可能性がある。
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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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2017~2019
課題番号 : 17K10152
研究分野 : 小児科学、腎臓学
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Mar 5, 2021 | | インデックス を変更 |
Nov 15, 2022 | | Creator Name,Creator Kana,Creator Romanization,Creator Affiliation,Creator Affiliation (Translated),Creator Role,Creator Link,Abstract 内容,Note 注記 を変更 |
Apr 12, 2024 | | Creator を変更 |
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