Transcriptome analysis of aldosterone-regulated genes in human vascular endothelial cell lines stably expressing mineralocorticoid receptor

稳定表达盐皮质激素受体的人血管内皮细胞系中醛固酮调节基因的转录组分析

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作者:Naoko Sekizawa, Takanobu Yoshimoto, Eri Hayakawa, Noriko Suzuki, Toru Sugiyama, Yukio Hirata

Abstract

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.

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