DNA methylation and hydroxymethylation in the kidney from offspring of nutrient restricted rats
Description: 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.
Amount: ¥4,680,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2017-04-01
End date: 2020-03-31
Investigator: Midori AWAZU
Institution: Keio University
Funded outputs count: 5
Funder award ID: 17K10152
OpenAlex ID: G3919048158