This SuperSeries is composed of the SubSeries listed below.
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesTo define the direct gene expression changes in normal human skeletal muscle with mineralocorticoid and glucocorticoid receptor agonist and antagonist treatment.
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesTo 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
Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists and antagonists on normal human skeletal muscle.
Sex, Specimen part
View SamplesThe 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.
Gene expression profile in rat adrenal zona glomerulosa cells stimulated with aldosterone secretagogues.
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View SamplesTo 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.
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sex
View SamplesTo identify the gene expression differences in skeletal muscles resulting from treatment of dystrophic mice with spironolactone plus lisinopril
Mineralocorticoid receptors are present in skeletal muscle and represent a potential therapeutic target.
Sex, Age, Treatment
View SamplesTarget gene of mineralocorticoid receptor (MR) is comparatively unknown, although distal convoluted tubule (DCT) expresses MR in in vivo.
Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor.
Cell line, Treatment
View SamplesIn 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-stimulating somatic gene mutations are common in normal adrenal glands.
Sex, Specimen part
View SamplesPURPOSE
Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer.
Specimen part, Disease
View SamplesPrimary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. Inactivation of Rarα in mice led to major structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA.
Retinoic acid receptor α as a novel contributor to adrenal cortex structure and function through interactions with Wnt and Vegfa signalling.
Sex, Age, Specimen part
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