Prevention of low nephron number by modulation of DNA methylation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461620
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: Awazu Midori 慶應義塾大学, 医学部(信濃町), 講師 (20129315)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

内科系臨床医学・小児科学