RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA687653 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:AngiotensinII (AngII) binds to the type I angiotensin receptor in the adrenal cortex to initiate a cascade of events leading to the production of aldosterone, a master regulator of blood pressure and volume. While the key signaling pathways, transcription factors, and steroidogenic enzymes necessary for adrenocortical production have been identified, surprisingly little is known about post-transcriptional regulation of this process. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response in a steroidogenic human cell line (H295R). We identified twelve temporally distinct groups of gene expression responses important for various steps of aldosterone production. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII or ACTH.
2021-06-01 | GSE163801 | GEO
Project description:Angiotensin II (AngII) stimulates adrenocortical cells to produce aldosterone, a master regulator of blood pressure. Despite extensive characterization of the transcriptional and enzymatic control of adrenocortical steroidogenesis, there are still major gaps in the precise regulation of AII-induced gene expression kinetics. Specifically, we do not know the regulatory contribution of RNA-binding proteins (RBPs) and RNA decay, which can control the timing of stimulus-induced gene expression. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response and 4-thiouridine pulse labeling in a steroidogenic human cell line (H295R). We identified twelve temporally distinct gene expression responses that contained mRNA encoding proteins known to be important for various steps of aldosterone production, such as cAMP signaling components and steroidogenic enzymes. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII. Using a candidate screen, we identified a subset of RNA-binding protein and RNA decay factors that activate or repress AngII-stimulated aldosterone production. Among the repressors of aldosterone were BTG2, which promotes deadenylation and global RNA decay. BTG2 was induced in response to AngII stimulation and promoted the repression of mRNAs encoding pro-steroidogenic factors indicating the existence of an incoherent feedforward loop controlling aldosterone homeostasis. These data support a model in which coordinated increases in transcription and decay facilitate the major transcriptomic changes required to implement a pro-steroidogenic expression program that actively resolved to prevent aldosterone overproduction.
| S-EPMC8284322 | biostudies-literature
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
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.
2015-06-12 | GSE69777 | 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:CRISPR/Cas9 screening of RNA binding proteins (RBPs) that regulate RUNX1 isoform production
| PRJNA608901 | ENA
Project description:The mineralocorticoid hormone, aldosterone, is secreted by the adrenal zona glomerulosa (ZG) in response to high plasma K+ and hypovolemia and promotes renal Na+ reabsorption and K+ secretion. Hence, the regulation of aldosterone secretion is critical for the control of ion homeostasis and blood pressure. While the kinase pathways regulating aldosterone production are well studied, little is known about the involved phosphatases. Using the human adrenocortical carcinoma cell line NCI-H295R, we found that the mRNA expression of the aldosterone synthase increases significantly within 6 hours after K+ exposure. This increase was inhibited in a dose-dependent manner by the calcineurin inhibitors tacrolimus and cyclosporine A. Calcineurin (Cn) is a serine-threonine-specific, Ca2+ and CaM-activated protein phosphatase essential for lymphocyte, neuronal and cardiac function. The physiologic role of Cn in the ZG cells and the molecular pathways by which Cn regulates the K+-stimulated secretion of aldosterone are unknown. To answer these questions, we stimulated NCI-H295R cells with K+ with or without Tacrolimus and studied the phosphorylation pattern of cytoplasmic proteins by phospho-proteomics. We generated a map of the changes in the Ser/Thr phosphorylation in adrenocortical cells upon stimulation with K+ and identified Cn-regulated phosphoproteins.
2023-05-25 | PXD027856 | Pride
Project description:RNA binding proteins in cancer spliceome
| PRJNA348692 | ENA
Project description:Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This experiment investigated of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared to those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified twelve genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1-3 hours after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart. Methods: Male C57BL6 mice were injected with aldosterone 10 mcg/kg (experimental group) or vehicle (control group) at time 0. Five animals were sacrificed at each of the following time points in each group: 0, 0.5, 1, 2, 3, 4, 5, and 12 hours from injection. Hearts were removed and total RNA extracted from the hearts of all five animals at each time point / experimental condition was pooled for gene expression analysis. Keywords: time series
2005-11-01 | GSE3440 | GEO
Project description:Aldosterone excess is involved in cardiac diseases. The mechanisms are still unclears. Mice were treated for 7 days with aldosterone and a whole genome microarray analysis was performed.
2016-09-08 | GSE50709 | GEO