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GSE29912
Rattus norvegicus
8 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
GLUCOCORTICOIDS are steroid hormones that strongly influence intermediary carbohydrate metabolism by increasing the transcription rate of glucose-6-phosphatase (G6Pase) a key enzyme of gluconeogenesis, and suppress the immune system which makes them one of the most important therapeutic agents in the treatment of allergic, autoimmune and inflammatory diseases. The biologic actions of circulating glucocorticoids are transmitted to the cells nucleus by the glucocorticoid receptor (GR). The nuclear liver X receptors (LXRs) bind to cholesterol metabolites, heterodimerize with the retinoid X receptor (RXR), and regulate the cholesterol turnover, the hepatic glucose metabolism by decreasing the expression of G6Pase, and repress a set of inflammatory genes in immune cells. The aim of this study is to evaluate the crosstalk between the GR- and LXR-mediated signaling systems. Transient transfection-based reporter assays and gene silencing methods using siRNAs for LXRs showed that overexpression/ligand (GW3965) activation of LXRs/RXRs repressed GR-stimulated transactivation of certain glucocorticoid response element (GRE)-driven promoters in a gene-specific fashion. Activation of LXRs by GW3965 attenuated dexamethasone-stimulated elevation of circulating glucose in rats and suppressed dexamethasone-induced mRNA expression of hepatic glucose-6-phosphatase (G6Pase) in rats, mice and human hepatoma HepG2 cells. In microarray transcriptomic analysis of rat liver, GW3965 differentially regulated glucocorticoid-induced transcriptional activity of about 15% of endogenous glucocorticoid-responsive genes. Mechanistically, and in vitro chromatin immunoprecipitation assay, we found that LXR/RXR bound GREs and inhibited GR binding to these DNA sequences in a gene-specific fashion. These novel results were further confirmed in in vivo binding assays, and in gel mobility shift assays, where recombinant LXR/RXR proteins were used to examine their interaction with classic or G6Pase GREs. We propose that administration of LXR agonists may be beneficial in glucocorticoid treatment- or stress-associated dysmetabolic states by directly attenuating the transcriptional activity of the GR on glucose and/or lipid metabolism.
Publication Title
Liver x receptors regulate the transcriptional activity of the glucocorticoid receptor: implications for the carbohydrate metabolism.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
To further understand molecular mechanisms underlying skeletal muscle hypertrophy, expression profiles of translationally and transcriptionally regulated genes were characterized following an acute bout of maximally activated eccentric contractions. Experiments demonstrated that translational mechanisms contribute to acute gene expression changes following high resistance contractions with two candidate mRNAs, basic fibroblast growth factor (bFGF) and elongation factor-1 alpha (EF1alpha), targeted to the heavier polysomal fractions after a bout of contractions. Gene profiling was performed using Affymetrix Rat U34A GeneChips with either total RNA or polysomal RNA at one and six hours following contractions. There were 18 genes that changed expression at one hour and 70 genes that were different (60 genes increased:10 genes decreased)at six hours after contractions. The model from this profiling suggests that following high resistance contractions skeletal muscle shares a common growth profile with proliferating cells exposed to serum. This cluster of genes can be classified as "growth" genes and is commonly associated with progression of the cell cycle. However, a unique aspect was that there was induction of a cluster of tumour suppressor or antigrowth genes. We propose that this cluster of "antigrowth" genes is induced by the stress of contractile activity and may act to maintain skeletal muscle in the differentiated state. From the profiling results, further experiments determined that p53 levels increased in skeletal muscle at 6 h following contractions. This novel finding of p53 induction following exercise also demonstrates the power of expression profiling for identification of novel pathways involved in the response to muscle contraction.
Publication Title
Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, while AMPK is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive GILZ, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Since increased action of glucocorticoids is associated with development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacologic interventions to these pathologies.
Publication Title
AMPK regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 MAPK.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this investigation was to evaluate the effect of training on the global transcriptional response of skeletal muscle to an acute bout of resistance exercise.
Publication Title
Resistance exercise training influences skeletal muscle immune activation: a microarray analysis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The purpose of the study was to detect the sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, resistance exericse.
Publication Title
Skeletal muscle gene expression in response to resistance exercise: sex specific regulation.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex.
Publication Title
Microarray analysis reveals novel features of the muscle aging process in men and women.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Bacterial control of host gene expression through RNA polymerase II.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation, in which the contrasting effects of pathogens and commensals on host tissues are clearly displayed. While virulent Escherichia coli cause severe, potentially life-threatening disease by breaking the inertia of the mucosal barrier and infecting the kidneys, the most common outcome of bacteriuria is an asymptomatic carrier state resembling commensalism at other mucosal sites. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease associated responses in the host. To address this question, we examined the effects of asymptomatic bacterial carriage on host gene expression.
Publication Title
Bacterial control of host gene expression through RNA polymerase II.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We demonstrated that deletion of the p53 tumor suppressor gene in NG2 expressing cells resulted in the development of bone and soft tissue sarcomas that closely resemble human tumors. To determine gene expression differences between NG2 expressing pericytes lacking p53 and sarcomas that arose from deletion of p53 in NG2 expressing cells, RNA sequencing analysis was implemented. Overall design: We isolated total RNA from NG2 expressing pericytes (2 samples), which were sorted from skeletal muscle tissues of NG2-Cre;p53flox/flox mice using an NG2 antibody. We also isolated total RNA from osteosarcomas (2 samples) and soft tissue sarcomas (2 samples), which were developed in NG2-Cre;p53flox/flox mice. Differentially expressed genes were analyzed using Illumina HiSeq 2000.
Publication Title
Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation, in which the contrasting effects of pathogens and commensals on host tissues are clearly displayed. While virulent Escherichia coli cause severe, potentially life-threatening disease by breaking the inertia of the mucosal barrier and infecting the kidneys, the most common outcome of bacteriuria is an asymptomatic carrier state resembling commensalism at other mucosal sites. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease associated responses in the host. To address this question, we examined the effects of asymptomatic bacterial carriage on host gene expression.
Publication Title
Bacterial control of host gene expression through RNA polymerase II.
Sample Metadata Fields
Cell line
View Samples