Rattus norvegicus
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PROVIDER: PRJNA101473 | ENA |
REPOSITORIES: ENA
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Project description:The mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex. Experiment Overall Design: Freshly isolated rat adrenal cells were treated with Ang II (100 nM) or potassium (16 mM) for 2 h at 37C. Experiment Overall Design: Total RNA from three independent experiments were isolated, labeled and hybridized to whole genome high-density oligonucleotide microarrays (Affymetrix Rat Genome 230 2.0). Experiment Overall Design: 3 independent cell preparations. Experiment Overall Design: In each experiement there is one tube control, one Ang II (100 nM) and potassium (16 mM).
2008-10-18 | E-GEOD-8421 | biostudies-arrayexpress
Project description:The mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex. Keywords: agent response
2008-06-29 | GSE8421 | GEO
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:The adrenal cortex is characterized by a distinct architecture as well as a high density of specialized sinusoidal blood vessels. The preservation of this particular endothelial cell phenotype is likely vital for proper adrenal gland function. The aldosterone-producing zona glomerulosa harbors macrophages in close association with sinusoidal capillaries. However, the function of this macrophage-endothelial cell-juxtaposition in steady-state conditions is unknown. We show that macrophages preserve capillary specialization in the adrenal gland and modulate aldosterone secretion. By combining macrophage-specific deletion of the angiogenic cytokine Vascular Endothelial Growth Factor A (VEGF-A), single-cell transcriptomics and functional phenotyping, we provide evidence that loss of VEGF-A in myeloid cells, including adrenal gland macrophages depletes a specialized subset of PLVAP+ fenestrated endothelial cells in the zona glomerulosa of mice, along with increased deposition of basement membrane collagen IV and in
2024-06-24 | GSE245128 | GEO
Project description:The adrenal cortex is characterized by a distinct architecture as well as a high density of specialized sinusoidal blood vessels. The preservation of this particular endothelial cell phenotype is likely vital for proper adrenal gland function. The aldosterone-producing zona glomerulosa harbors macrophages in close association with sinusoidal capillaries. However, the function of this macrophage-endothelial cell-juxtaposition in steady-state conditions is unknown. We show that macrophages preserve capillary specialization in the adrenal gland and modulate aldosterone secretion. By combining macrophage-specific deletion of the angiogenic cytokine Vascular Endothelial Growth Factor A (VEGF-A), single-cell transcriptomics and functional phenotyping, we provide evidence that loss of VEGF-A in myeloid cells, including adrenal gland macrophages depletes a specialized subset of PLVAP+ fenestrated endothelial cells in the zona glomerulosa of mice, along with increased deposition of basement membrane collagen IV and induction of sub-endothelial fibrosis.
2024-06-24 | GSE245127 | GEO
Project description:Transcriptome profile of rat adrenal evoked by gonadectomy and testosterone or estradiol replacement
| PRJNA362207 | ENA
Project description:The human adrenal gland consists of concentrically organized functionally distinct regions responsible for hormone production. Dysregulation of adrenocortical cell differentiation alters the proportion and organization of the functional zones of the adrenal cortex leading to disease. Current models of adrenocortical cell differentiation are based on mouse studies, but there are known organizational and functional differences between human and mouse adrenal glands. This study aimed to investigate the centripetal differentiation model in the human adrenal cortex and characterize aldosterone-producing micronodules (APMs) to better understand adrenal diseases such as primary aldosteronism. We applied spatially resolved in situ transcriptomics to human adrenal tissue sections from two individuals and identified distinct cell populations and their positional relationships. The results supported the centripetal differentiation model in humans, with cells progressing from the outer capsule to the zona glomerulosa, zona fasciculata, and zona reticularis. Additionally, we characterized two APMs in a 72-year-old female. Comparison with earlier APM transcriptomes indicated a subset of core genes, but also heterogeneity between APMs. The findings contribute to our understanding of normal and pathological cellular differentiation in the human adrenal cortex.
2023-11-15 | GSE244084 | GEO
Project description:Human aldosterone producing cell clusters, zona glomerulosa, zona fasciculata, and zona reticularis, from adrenal glands
| PRJNA283974 | ENA
Project description:In order to analyze the transcriptome characteristics of aldosterone producing cell clusters (APCC) we compared transcript abundances of APCC, zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR), from adrenal glands obtained from 4 kidney transplantation donors. The frozen adrenal glands in O.C.T. compound were cut into 7um sections, and every 10-th section immunostained for aldosterone synthase (CYP11B2). The remaining sections were stained with cresyl violet and used for laser-capture microdissection of tissue to use in the array assays. APCC and ZG samples were captured from CYP11B2 positive regions based on the CYP11B2-stained sections. ZF and ZR were captured from lipid-rich cells in the middle layer and compact cells outside of the medulla, respectively. RNA was isolated using PicoPure RNA isolation kits (Molecular Devices, Sunnyvale, CA). 1-10 ng total RNA was reverse-transcribed and amplified with the Ovation Pico WTA System V2 (NuGEN Technologies, San Carlos, CA). cDNA was purified using QIAquick PCR Purification Kit (Qiagen, Hilden, Germany) and biotin-labeled using Encore Biotin Module (NuGEN Technologies), followed by hybridization to GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Expression values were calculated using the robust multi-array average method (RMA). This resulted in base-2 log-transformed data for each of the 4 tissues from each of the 4 people. In addition to the raw and processed data we also supply a supplementary Excel file holding the data and some statistical analysis, which has features to make simple graphs, and holds probe-set annotation that we used at that time (users may wish to obtain new annotation though). We fit two-way ANOVA models with terms for 4 tissues and 4 people, and compared each probe-set between every pair of tissues using F-tests for pairwise contrasts. We modeled people effects since they were not negligible. The supplement shows how to calculate the tests. Aldosterone producing cell clusters (APCC), zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR), from adrenal glands obtained from 4 kidney transplantation donors, were individually assayed on 16 Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. Expression values were estimated with the Robust Multi-Arry average (RMA) algorithm, which resulted in log-2 transformed values for each of 54675 probe sets.
2015-06-26 | E-GEOD-68889 | biostudies-arrayexpress