Project/Area Number |
23591584
|
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, 講師 (20129315)
|
Co-Investigator(Kenkyū-buntansha) |
HIDA Mariko 慶應義塾大学, 医学部, 共同研究員 (20276306)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | 小児腎・泌尿器学 / 尿管芽分岐 / 母体低栄養 / DNAメチル化 / 子宮内環境 / ネフロン数 / DNAメチル化酵素 / 尿管芽 / カスパーゼ3 / Wnt11 / ベータカテニン / シグナル伝達 / 母低ステロイド / カスパーゼ3 / 細胞運動 / DOHaD |
Research Abstract |
Low nephron number increases the risk of chronic kidney disease. Nephron number is determined by intrauterine environment. We studied the mechanisms of low nephron number and reduced ureteric bud branching by maternal nutrient restriction in rats, and found that caspase-3, a cysteine protease, is playing an important role. We attempted to increase nephron number by giving lithium, an agent to activate b-catenin, a molecule downstream of caspase-3. Due to toxicity, however, this approach turned out to be unsuccessful. We investigated the effects of maternal nutrient restriction on genome-wide DNA methylation in rat embryonic kidney. Methylated genes by nutrient restriction important in kidney development are mostly those critical for ureteric branching. Targeting DNA methylation could lead to a new therapeutic strategy.
|