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GSE11393
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Introduction: The genetic origin of familial combined hyperlipidemia (FCH) is not well understood. We used microarray profiling of peripheral blood monocytes to search novel genes and pathways involved in FCH. Methods: Fasting plasma for determination of lipid profiles, inflammatory molecules, and adipokines was obtained and peripheral blood monocytes were isolated from male FCH patients basally and after 4 weeks of atorvastatin treatment. Sex-, age- and adiposity-matched controls were also studied. Gene expression profile was analyzed using Affymetrix Human Genome U133A 2.0 GeneChip arrays. Results: Analysis of gene expression by cDNA microarrays showed that 82 genes were differentially expressed in FCH monocytes compared to controls. Atorvastatin treatment modified the expression of 87 genes. Changes in the expression of some genes, confirmed by real time RT-PCR, (CD36, leucine-rich repeats and immunoglobulin-like domains-1, tissue factor pathway inhibitor 2, myeloid cell nuclear differentiation antigen tumor necrosis factor receptor superfamily, member 25 and CD96) may be related to a proinflammatory environment in FCH monocytes, which is partially reversed by atorvastatin. Higher plasma levels of triglycerides and free fatty acids and lower levels of adiponectin in FCH patients could also trigger changes in gene expression that atorvastatin cannot modify. Conclusions: Our results demonstrate clear differences in gene expression in FCH monocytes compared with those of matched healthy controls, some of which are influenced by atorvastatin treatment.
Publication Title
Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH.
Publication Title
Molecular interplay between Δ5/Δ6 desaturases and long-chain fatty acids in the pathogenesis of non-alcoholic steatohepatitis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 162 Downloadable Samples
IlluminaHiSeq2500
Description
Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming, we treated zebrafish embryos with cortisol and examined the effects on adults. In adulthood, the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity. Overall design: 30 samples total were analyzed. 9 caudal fins samples (0, 2 and 4dpa), 3 blood samples and 3 muscle samples from adults exposed to DMSO control as embryos. 9 caudal fins samples (0, 2 and 4dpa), 3 blood samples and 3 muscle samples from adults exposed to cortisol (1 micromolar) as embryos.
Publication Title
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to characterize gene expression networks linked to AT1 angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1A receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. At baseline, 405 genes were differentially expressed (>1.5X) between WT and KO kidneys. Of these, more than 80% were up-regulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ~805 genes was altered (18% up-regulated, 82% repressed). Genes in metabolism and ion transport pathways were up-regulated while there was attenuated expression of protective genes against oxidative stress including glutathione synthetase and mitochondrial SOD2. Angiotensin II infusion has little effect on blood pressure in KOs. Nonetheless, expression of more than 250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were up-regulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation.
Publication Title
Gene expression profiles linked to AT1 angiotensin receptors in the kidney.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Chronic early life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with 1 micromolar cortisol and examined the effects on larvae. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and up-regulated genes associated with defense response and immune system processes. Overall design: 6 samples total were analyzed. 3 DMSO controls, and 3 cortisol treated (1 micromolar).
Publication Title
Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53 and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell cycle arrest, apoptosis, and p53-target gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.
Publication Title
The WTX tumor suppressor enhances p53 acetylation by CBP/p300.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 16 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors repressed FOXO.
Publication Title
The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
Publication Title
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The human SYT-SSX fusion protein was expressed in a developmentally dependent fashion in murine myoblasts. Tumors harvested from mice in adolescence were compared to normal mouse skeletal muscle samples.
Publication Title
A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
Sample Metadata Fields
No sample metadata fields
View Samples