Transcriptome analysis of aldosterone-regulated genes in human vascular endothelial cell lines stably expressing mineralocorticoid receptor
Transcriptome analysis of aldosterone-regulated genes in human vascular endothelial cell lines stably expressing mineralocorticoid receptor
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DOI：
10.1016/j.mce.2011.05.029
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发表时间：
2011-07
影响因子：
4.1
通讯作者：
Naoko Sekizawa;T. Yoshimoto;Eri Hayakawa;N. Suzuki;Toru Sugiyama;Y. Hirata
中科院分区：
文献类型：
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作者：
Naoko Sekizawa;T. Yoshimoto;Eri Hayakawa;N. Suzuki;Toru Sugiyama;Y. Hirata
一系列研究表明，内皮细胞是醛固酮作用的靶组织之一。在这里，我们已经进行了醛固酮诱导基因的转录组分析稳定表达人盐皮质激素受体（MR）的逆转录病毒系统（MR-EAhy）的人内皮细胞系。我们发现生理浓度的醛固酮在MR-EAhy中强烈诱导MR依赖性转录反应。通过DNA微阵列分析，我们验证了12个醛固酮上调基因，其中至少有7个伴随着蛋白质表达增加。我们还发现了5个醛固酮下调基因。在检测的11个醛固酮上调基因中，有3个（ESM 1，SNF 1 LK，ANGPTL 4）的mRNA表达在醛固酮诱导的高血压大鼠主动脉组织中较对照组显著上调，提示其在体内可能具有病理生理意义。总之，使用MR稳定表达的人内皮细胞系，我们确定了各种醛固酮诱导的基因，这表明它们可能在醛固酮诱导的血管损伤的发展和/或保护中的作用。
A series of studies have demonstrated that endothelial cell is one of the target tissues of aldosterone. Here, we have conducted a transcriptome analysis of aldosterone-inducible genes in human endothelial cell lines stably expressing human mineralocorticoid receptor (MR) by retroviral system (MR-EAhy). We found that aldosterone in physiologic concentrations robustly induced MR-dependent transcriptional response in MR-EAhy. By DNA microarray analysis, we validated 12 aldosterone-up-regulated genes among which at least seven were concomitantly associated with increased protein expression. We also found five aldosterone-down-regulated genes. Among 11 aldosterone-up-regulated genes tested, mRNA expressions of three (ESM1, SNF1LK, ANGPTL4) were significantly up-regulated in aortic tissue from aldosterone-induced hypertensive rats compared to those from control rats, suggesting their potential pathophysiologic significance in vivo. In conclusion, using MR stably expressed human endothelial cell lines, we identified a variety of aldosterone-inducible genes, suggesting their possible roles in the development and/or the protection for aldosterone-induced vascular injury.