Maternal Undernourished Fetal Kidneys Exhibit Differential Regulation of Nephrogenic Genes Including Downregulation of the Notch Signaling Pathway
Maternal Undernourished Fetal Kidneys Exhibit Differential Regulation of Nephrogenic Genes Including Downregulation of the Notch Signaling Pathway
复制标题
DOI：
10.1177/1933719110393025
复制
发表时间：
2011-06-01
影响因子：
2.9
通讯作者：
Nast, Cynthia C.
中科院分区：
文献类型：
--
作者：
Magee, Thomas R.;Tafti, Sanaz A.;Nast, Cynthia C.
母体营养不良导致后代肾单位数量减少和高血压，这被假设为开始作为妊娠期间胎儿基因表达的代偿性变化。为了评价肾发生失调的机制，妊娠Sprague道利大鼠从胚胎第10天（E）至E20天限制50%食物。在E20，通过微阵列分析检查胎儿男性肾脏。共检测到476个差异表达的转录本，包括调节发育和分化、有丝分裂和细胞周期、染色质组装和类固醇激素调节的转录本。在MAPK/ERK、Wnt和Notch信号通路中检测到差异调节基因。对Notch信号通路（肾单位形成中的重要通路）进行微阵列结果的验证。通过Western印迹分析Notch途径因子的蛋白表达显示Notch 2和下游效应子Hey 1蛋白表达显著降低，而Ctbp 1辅阻遏物增加。这些数据共同表明，母体营养不良导致胎儿肾发生基因表达信号传导的发育中断。
Maternal undernutrition results in offspring nephron number reduction and hypertension that are hypothesized to begin as compensatory changes in fetal gene expression during gestation. To evaluate mechanisms of dysregulated nephrogenesis, pregnant Sprague Dawley rats were 50% food restricted from embryonic day (E) 10 to E20. At E20, fetal male kidneys were examined by microarray analysis. A total of 476 differentially expressed transcripts were detected including those regulating development and differentiation, mitosis and cell cycle, chromatin assembly, and steroid hormone regulation. Differentially regulated genes were detected in MAPK/ERK, Wnt, and Notch signaling pathways. Validation of the microarray results was performed for the Notch signaling pathway, an important pathway in nephron formation. Protein expression of Notch pathway factors by Western blotting showed significantly decreased Notch2 and downstream effector Hey1 protein expression, while Ctbp1 co-repressor was increased. These data together show that maternal undernutrition results in developmental disruption in fetal nephrogenesis gene expression signaling.