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GSE2880
Rattus norvegicus
62 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Epilepsy is a major neurological disorder that affects approximately 1% of the population. The processes that lead to the development of epilepsy (epileptogenesis) are largely unknown. Levetiracetam is a novel antiepileptic drug (AED) that in the kindling model inhibits epileptogenesis in addition to being effective in controlling established epilepsy. The mechanisms of action of levetiracetam as an AED and an antiepileptogenic drug are unknown. By identifying the effect of chronic levetiracetam therapy on gene expression in the brain we hope to be able to identify genes that are involved in epileptogenesis. By comparing the gene expression profiles of levetiracetam and phenytoin treatments, we hope to be able to distinguish between genes that are important for the antiepileptic (anti-seizure) effect and genes that are important for the antiepileptogenic effect of levetiracetam. Phenytoin is a well-established AED; its mechanism of action involves inhibition of sodium channels. In contrast to levetiracetam, available data suggest that phenytoin in certain situations may enhance rather than inhibit the development of epilepsy.
Publication Title
Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analysis and identified 366 genes with altered expression in four unique tamoxifen resistant (TamR) cell lines vs the parental tamoxifen sensitive MCF7/S0.5 cell line. Most of these genes were funcationally linked to cell proliferation, death and control gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF7/S0.5 cells. Moreover, overexpression of FYN in parental tamoxifen-sensitive MCF7/S0.5 cells resulted in reduced sensitivity to tamoxifen, demonstrating growth and survival promoting function of FYN in MCF7 cells. FYN knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and CDc 25A, suggesting that FYN, by activation of of important cell cycle-associated proteins, may overcome the anti-proliferative effects of tamoxifen. Evaluation of the subcellular localization of FYN in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N = 47) and the other with early disease (N = 76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P<0.0002). Similarly, in early breast cancer patients, membrane-associated expression of FYN in the primary breast tumor was significantly associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival independent of tumor size, grade or lymph node status. Our results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer.
Publication Title
Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown.
Publication Title
Vitamin D metabolites influence expression of genes concerning cellular viability and function in insulin producing β-cells (INS1E).
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Time-series analysis of response to ribosome 28s damage at gene expression level
Publication Title
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The role of PPAR in gene regulation in mouse liver is well characterized. However, less is known about the effect of PPAR activation in human liver. The aim of the present study was to better characterize the impact of PPAR activation on gene regulation in human liver by combining transcriptomics with the use of hepatocyte humanized livers. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analysed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on fenofibrate treatment in normal mice. The human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPAR targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P<0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPAR targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver. The results support the major role of PPAR in regulating hepatic lipid metabolism, and underscore the more modest effect of PPAR activation on gene regulation in human liver compared to mouse liver. The data suggest that PPAR may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.
Publication Title
The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sample Metadata Fields
Sex, Disease, Subject, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. Results: To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Methods: Cold acclimation altered the expression of 756 genes (422 up, 334 down, P<0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P<0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Conclusions: Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to cell remodeling rather than metabolic pathways.
Publication Title
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sample Metadata Fields
Sex, Disease, Subject, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. Results: To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Methods: Cold acclimation altered the expression of 756 genes (422 up, 334 down, P<0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P<0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Conclusions: Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to cell remodeling rather than metabolic pathways.
Publication Title
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sample Metadata Fields
Sex, Disease, Subject, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Publication Title
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.
Sample Metadata Fields
Sex, Specimen part
View Samples