This SuperSeries is composed of the SubSeries listed below.
Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.
Sex, Specimen part
View SamplesTelomere dysfunctional CMP/GMP have deregulated pathways that are associated with DNA damage signaling
Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.
Sex, Specimen part
View SamplesPancreatic islets are central in type 2-diabetes development, which coincides with increased activity of innate immunity. Intriguingly, human pancreatic islets express many complement genes. The most highly expressed gene was the complement inhibitor CD59 that is GPI anchored to the cell membrane, which unexpectedly was found in high amounts intracellularly in beta cells. Silencing of CD59 strongly suppressed insulin secretion. Importantly, this suppression was unrelated to established CD59 functions, but rather depletion of intracellular CD59. Imaging experiments identified a distal site of inhibition in the exocytotic pathway, but prior to emptying of the insulin granules. Proximity Ligation Assays pin-pointed the mechanism to impaired turnover of exocytosis-regulating SNARE-proteins and CD59 was detected in complex with VAMP2 and syntaxin. CD59 was downregulated by 24-h glucose incubations in human islets, rat cell lines and in islets from three rodent diabetes models.
The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events.
Specimen part
View SamplesThis 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 SamplesPURPOSE
Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer.
Specimen part, Disease
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
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