Differential antagonistic effects of finerenone and spironolactone on the aldosterone transcriptome in human kidney cells.
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PROVIDER: PRJNA635433 | ENA |
REPOSITORIES: ENA
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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.
2022-05-09 | GSE151321 | GEO
Project description:Kidney distal convoluted tubules (DCT) are important for regulation of urinary salt excretion. Aldosterone is known to exert long-term effects in this segment, and regulate sodium reabsorption via increasing abundance of the Na+-Cl- cotransporter (NCC) and the epithelial Na channel ENaC. Whether acute effects of aldosterone occur in the DCT and the potential signaling networks remain unknown. Here in this study, we aim to identify the acute aldosterone-mediated signaling (rapid effects) in the DCT.
2019-06-24 | PXD010032 | Pride
Project description:To uncover whether aldosterone induces gene expression changes through mineralocorticoid or glucocorticoid receptors and determine if eplerenone and spironolactone could block aldosterone induced gene expression to the same extent
2017-05-05 | GSE84991 | GEO
Project description:Aldosterone is arguably the single most important hormone implicated in the control of blood pressure and extracellular fluid volume in mammals. It acts primarily by increasing the rate of transepithelial sodium transport in the kidney tubules. Several monogenetic defects resulting in hypertension have now been attributed to abnormalities in sodium handling within the aldosterone-sensitive distal nephron, where the epithelial sodium channel, ENaC, constitutes the rate-limiting step of sodium transport. To date, the transcription-dependent aldosterone-signaling pathway between receptor and membrane transport effectors, remains incompletely understood. The broad aim of our study is to explore these intracellular signaling pathways that are critical to the functioning of sodium channels. Microarray analysis in an aldosterone-responsive kidney cortical collecting duct cell line (mpkCCDc14), allowed us to identify many potential aldosterone-regulated transcripts. The present study describes the identification, and possible physiological relevance of various aldosterone-regulated transcripts. The results of this study promise to extend our understanding of the molecular basis of aldosterone-regulated sodium transport in kidney epithelia, and provide approaches for regulating this process in disease states such as congestive heart failure and hypertension. Keywords: hormone effect
2005-07-15 | GSE2933 | GEO
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. Wild type C57Bl6 male mice were treated with spironolactone (20 mg/kg/day, an MR antagonist) for 5 days by Sub-cutaneous pellet to suppress basal MR-mediated gene expression. Aortas were then harvested and treated ex vivo in organ culture with vehicle or 100 nM aldosterone for 2, 4, or 8 hours. Three aortas were pooled for each timepoint and treatment, and three pooled biological replicates were performed.
2010-08-12 | E-GEOD-23566 | biostudies-arrayexpress
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.
2015-07-14 | E-GEOD-70822 | biostudies-arrayexpress
Project description:In this study, we analyzed the transcriptome of a highly differentiated mouse clonal CCD principal cell line (mpkCCD(cl4)) and the changes in the transcriptome induced by aldosterone and vasopressin. Serial analysis of gene expression (SAGE) was performed on untreated cells and on cells treated with either aldosterone or vasopressin for 4 h. The transcriptomes in these three experimental conditions were determined by sequencing 169,721 transcript tags from the corresponding SAGE libraries. Limiting the analysis to tags that occurred twice or more in the data set, 14,654 different transcripts were identified, 3,642 of which do not match known mouse sequences. Statistical comparison (at P < 0.05 level) of the three SAGE libraries revealed 34 AITs (aldosterone-induced transcripts), 29 ARTs (aldosterone-repressed transcripts), 48 VITs (vasopressin-induced transcripts) and 11 VRTs (vasopressin-repressed transcripts). A selection of the differentially-expressed, hormone-specific transcripts (5 VITs, 2 AITs and 1 ART) has been validated in the mpkCCD(cl4) cell line either by Northern blot hybridization or reverse transcription-PCR. The hepatocyte nuclear transcription factor HNF-3-alpha (VIT39), the receptor activity modifying protein RAMP3 (VIT48), and the glucocorticoid-induced leucine zipper protein (GILZ) (AIT28) are candidate proteins playing a role in physiological responses of this cell line to vasopressin and aldosterone. Keywords: other
2003-09-24 | E-GEOD-678 | biostudies-arrayexpress
Project description:In this study, we analyzed the transcriptome of a highly differentiated mouse clonal CCD principal cell line (mpkCCD(cl4)) and the changes in the transcriptome induced by aldosterone and vasopressin. Serial analysis of gene expression (SAGE) was performed on untreated cells and on cells treated with either aldosterone or vasopressin for 4 h. The transcriptomes in these three experimental conditions were determined by sequencing 169,721 transcript tags from the corresponding SAGE libraries. Limiting the analysis to tags that occurred twice or more in the data set, 14,654 different transcripts were identified, 3,642 of which do not match known mouse sequences. Statistical comparison (at P < 0.05 level) of the three SAGE libraries revealed 34 AITs (aldosterone-induced transcripts), 29 ARTs (aldosterone-repressed transcripts), 48 VITs (vasopressin-induced transcripts) and 11 VRTs (vasopressin-repressed transcripts). A selection of the differentially-expressed, hormone-specific transcripts (5 VITs, 2 AITs and 1 ART) has been validated in the mpkCCD(cl4) cell line either by Northern blot hybridization or reverse transcription-PCR. The hepatocyte nuclear transcription factor HNF-3-alpha (VIT39), the receptor activity modifying protein RAMP3 (VIT48), and the glucocorticoid-induced leucine zipper protein (GILZ) (AIT28) are candidate proteins playing a role in physiological responses of this cell line to vasopressin and aldosterone. Keywords: other
2003-09-24 | GSE678 | GEO
Project description:Murine inner medullary collecting duct cells were treated for 1 hour with vehicle (control) or aldosterone. Total RNA was isolated and used as template to generate the eventual cRNA target. The experiment was repeated a total of three times. Six cRNA samples, three control and three treated, were generated and used in a total of six hybridizations. The mineralocorticoid aldosterone is a major regulator of Na+ and acid-base balance and control of blood pressure. Although the long-term effects of aldosterone have been extensively studied, the early aldosterone-responsive genes remain largely unknown. Using DNA array technology, we have characterized changes in gene expression after 1 h of exposure to aldosterone in a mouse inner medullary collecting duct cell line, mIMCD-3. Results from three independent microarray experiments revealed that the expression of many transcripts was affected by aldosterone treatment. Northern blot analysis confirmed the upregulation of four distinct transcripts identified by the microarray analysis, namely, the serum and glucose-regulated kinase sgk, connective tissue growth factor, period homolog, and preproendothelin. Immunoblot analysis for preproendothelin demonstrated increased protein expression. Following the levels of the four transcripts over time showed that each had a unique pattern of expression, suggesting that the cellular response to aldosterone is complex. The results presented here represent a novel list of early aldosterone-responsive transcripts and provide new avenues for elucidating the mechanism of acute aldosterone action in the kidney.
2007-11-06 | E-GEOD-434 | biostudies-arrayexpress
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.
2015-06-12 | E-GEOD-69777 | biostudies-arrayexpress