DNA methylation profiling in cell models of diabetic nephropathy
DNA methylation profiling in cell models of diabetic nephropathy
复制标题
DOI：
10.4161/epi.5.5.12077
复制
发表时间：
2010-07-01
期刊：
影响因子：
3.7
通讯作者：
Savage, David A.
中科院分区：
文献类型：
--
作者：
Brennan, Eoin P.;Ehrich, Mathias;Savage, David A.
我们先前已经在糖尿病肾病细胞模型和肾活检中鉴定了差异表达的基因。在这里，我们在糖尿病肾病的细胞模型中进行了定量DNA甲基化分析。与暴露于适当刺激的人系膜细胞（HMC）或近端肾小管上皮细胞（PTC）相比，在未刺激的人系膜细胞（HMC）和近端肾小管上皮细胞（PTC）中评估了192个候选基因的启动子区域中超过3，000个CpG单位。在38个基因中总共有301个CpG单位（类似于20%）被鉴定为在未刺激的HMC与PTC中差异甲基化。在未刺激与刺激的细胞模型中的扩增子甲基化值的分析未能证明扩增子之间的差异>20%。总之，我们的研究结果表明，特定的DNA甲基化特征存在于HMC和PTC中，并且将肾细胞暴露于改变基因表达的刺激的标准方案可能不足以复制糖尿病肾病中DNA甲基化谱的可能改变。
We have previously identified differentially expressed genes in cell models of diabetic nephropathy and renal biopsies. Here we have performed quantitative DNA methylation profiling in cell models of diabetic nephropathy. Over 3,000 CpG units in the promoter regions of 192 candidate genes were assessed in unstimulated human mesangial cells (HMCs) and proximal tubular epithelial cells (PTCs) compared to HMCs or PTCs exposed to appropriate stimuli. A total of 301 CpG units across 38 genes (similar to 20%) were identified as differentially methylated in unstimulated HMCs versus PTCs. Analysis of amplicon methylation values in unstimulated versus stimulated cell models failed to demonstrate a >20% difference between amplicons. In conclusion, our results demonstrate that specific DNA methylation signatures are present in HMCs and PTCs, and standard protocols for exposure of renal cells to stimuli that alter gene expression may be insufficient to replicate possible alterations in DNA methylation profiles in diabetic nephropathy.