Project description:To elucidate the aldosterone-regulated genes in vascular endothelial cells, we developed human endothelial cell line (EAhy926) stably expressing human mineralocorticoid receptor by retroviral system (MR-EAhy). Then gene expression profile of MR-EAhy stimulated with or without aldosterone was compared using DNA microarray analysis.
Project description:To elucidate the aldosterone-regulated genes in vascular endothelial cells, we developed human endothelial cell line (EAhy926) stably expressing human mineralocorticoid receptor by retroviral system (MR-EAhy). Then gene expression profile of MR-EAhy stimulated with or without aldosterone was compared using DNA microarray analysis. MR-EAhy were serum-deprived for 24h with 0.2% dextran-coated charcoal-treated FBS, and then stimulated with or without aldosterone (10-9 M) for 6 hr. Then cells were harvested for RNA extraction.
Project description:Aldosterone, the main mineralocorticoid hormone in Humans, has a major role in maintaining the hemo-electrolytique homeostasis, by acting in the distal part of nephron. This steroid hormone mainly acts through its binding to a ligand-induced transcription factor, the mineralocorticoid receptor (MR). MR binds to specific genomic sequences, where it recruits transcriptional coregulators, to activate or repress target gene transcription. The aim of this work was to access the whole aldosterone-dependand MR target genes, by comparing sequenced data from aldosterone or vehicle-treated samples. Anti-MR ChIP-seq in Human Kidney GFP-hMR cells treated with vehicle or Aldosterone.
Project description:Target gene of mineralocorticoid receptor (MR) is comparatively unknown, although distal convoluted tubule (DCT) expresses MR in in vivo. We used microarray and immortalized murine DCT cell-line overexpressing human MR with treatment of aldosterone to elucidate target genes of MR in DCT. mDCT overexpresses human MR by lipofection and is treated for 3 hours with ethanol (g1), or 10^-9 M aldosterone (g2), or 10^-7 M aldosterone (g3), or 10^-7 M aldosterone with pretreatment of 5 x 10^-6 M spironolactone (g4) for 2 hours.
Project description:Aldosterone, the main mineralocorticoid hormone in humans, controls, via gene transregulation, various renal functions including water and sodium reabsorption and potassium excretion. Dysregulations in the aldosterone signaling pathway lead to renal dysfunctions, including chronic kidney disease and renal fibrosis, that can be prevented or treated with mineralocorticoid receptor antagonists (MRAs). To understand the global effects of aldosterone on the human renal transcriptome, and how it is antagonized by the MRAs spironolactone and finerenone, we used RNA-sequencing on a human kidney cells HK-GFP-hMR. Our data provide the first complete transcriptome for aldosterone on a human renal cell line and support at the RNA level the benefit of finerenone for the treatment of kidney injury and fibrosis.
Project description:The mineralocorticoid receptor is expressed in the rat and human retina. We previously showed that intravitreal injection of aldosterone in rat eyes induced retinal œdème and choroidal vasodilation and permeability through regulation of ion/water channels (Zhao et al. Faseb J, 2009; Zhao et al. J Clin Invest 2012). Illicit activation of MR induces inflammation, oxidative stress and tissue remodeling in cardiovascular and renal diseases independent of hypertension. We performed a full transcriptomic study destinated to identify genes regulated by aldosterone in the whole retina of rat.
Project description:Target gene of mineralocorticoid receptor (MR) is comparatively unknown, although distal convoluted tubule (DCT) expresses MR in in vivo. We used microarray and immortalized murine DCT cell-line overexpressing human MR with treatment of aldosterone to elucidate target genes of MR in DCT.
Project description:The steroid hormone aldosterone plays a role in vascular function and disease. Aldosterone activates the mineralocorticoid receptor (MR), a ligand-activated transcription factor. MR have been found to be expressed in vascular cells and vessels. We used microarrays to identify the global programme of gene expression changes in mouse aortas treated with vehicle (DMSO) or aldosterone.
Project description:To test for a function effect of mineralocorticoid receptor modulation in skeletal muscle, global gene expression analysis was conducted on human myltubes treated with a mineralocorticoid receptor agonist or antagonist. 9 total samples were analyzed. 3 biological replicates for each of the following treatment groups were included: 1) aldosterone; 2) spironolactone; 3) vehicle (ethanol). Pairwise comparison between groups were carried out and a fold-change ≥2 were selected.
Project description:Atrial fibrillation is associated with stuctural remodelling of the atria that involves various cell types, including cardiac myocytes, endothelial cells, and immune cells. Atrial myopathy forms the substrate for an increased risk for AF onset and on the other hand AF drives atrial myopathy. Atrial myopathy is linked to risk factors such as aging, hypertension, obesity, or heart failure. Aldosterone and the mineralocorticoid receptor are drivers of pathological remodeling in atrial myopathy. In this study, we investigated the effect of aldosterone on left atrial gene expression and cell-cell communication.
