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

• Published in: Molecular and cellular endocrinology Vol. 341; no. 1; pp. 78 - 88
• Main Authors: Sekizawa, Naoko, Yoshimoto, Takanobu, Hayakawa, Eri, Suzuki, Noriko, Sugiyama, Toru, Hirata, Yukio
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 20.07.2011
• Subjects: Aldosterone; Aldosterone - pharmacology; Aldosterone - physiology; Animals; Aorta - drug effects; Aorta - metabolism; Cell Line; DNA microarrays; Endothelial cell; endothelial cells; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Gene Expression; gene expression regulation; Genes; Genes, Reporter; Humans; Hypertension - chemically induced; Hypertension - metabolism; Luciferases, Firefly - biosynthesis; Luciferases, Firefly - genetics; messenger RNA; microarray technology; Mineralocorticoid receptor; Mineralocorticoid Receptor Antagonists - pharmacology; mineralocorticoid receptors; Oligonucleotide Array Sequence Analysis; protein synthesis; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid - metabolism; Spironolactone - pharmacology; tissues; transcription (genetics); Transcriptome; transcriptomics; Endothelial cell; Aldosterone; Gene expression; Mineralocorticoid receptor
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2011.05.029

► We established human endothelial cell lines (MR-EAhy) stably expressing human MR cDNA. ► DNA microarray analysis identified seven aldosterone-upregulated-genes in MR-EAhy. ► ESM1, SNF1LK, and ANGPTL4 were upregulated in aldosterone-excess in vivo model. ► These genes are candidate playing potential role in aldosterone-induced vascular injury. 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.