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GSE63457
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to a model hepatotoxicant cyclosporin A (CsA). It was anticipated that Fxr deficiency could aggravate toxicity of CsA in PCLS and pinpoint to novel genes/processes regulated by FXR.
Publication Title
Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Beneficial microbes can be actors in maintaining or stimulating barrier function, and may counteract pathogen-infection. Lactobacilli are particularly recognized for enhancing intestinal barrier function and to confer protective effects against multiresistant pathogens. Various L. acidophilus strains support intestinal immune barrier function and have been shown to improve resistance to pathogens. Although less extensively studied than beneficial bacteria, other food-based ingredients that can contribute to strengthening barrier function are dietary fibers. For instance, inulin and fructooligosaccharides (FOS) have recently been shown to enhance barrier function and protect against barrier dysfunction. Effects of these ingredients on intestinal barrier function were evaluated by quantifying regulation of gene expression by microarray. Methods: Caco-2 cells were incubated with probiotic strains or inulin-type fibers for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. Results: Only L. acidophilus modulated a group of 26 genes related to tight-junctions. Inulin-type fructans, L. brevis W63 and L. casei W56 regulated other genes, unrelated to tight junctions. L. acidophilus also had unique effects on a group of 6 genes regulating epithelial phenotype towards follicle-associated epithelium. L. acidophilus W37 was therefore selected for a challenge with STM and prevented STM-induced barrier disruption and decreased secretion of IL-8. L. acidophilus W37 increases TEER and can protect against STM induced disruption of gut epithelial cells integrity in vitro. Conclusion: Our results suggest that selection of specific bacterial strains for enforcing barrier function may be a promising strategy to reduce or prevent STM infections.
Publication Title
<i>Lactobacillus acidophilus</i> Attenuates <i>Salmonella</i>-Induced Stress of Epithelial Cells by Modulating Tight-Junction Genes and Cytokine Responses.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of food compounds on (intestinal) health. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were incubated with in vitro digested onion extracts for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify onion-induced gene expression profiles in Caco-2 cells, digested yellow onion and white onion samples were compared to a digest control samples. Results: We found that yellow onion (n=5586, p<0.05) had a more pronounced effect on gene expression than white onion (n=3688, p<0.05). However, a substantial number of genes (n=3281, p<0.05) were affected by both onion variants in the same direction. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Conclusion: our data indicate that the in vitro Caco-2 intestinal model can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.
Publication Title
Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and non-immunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (i) with structural similarities, such as the tributyltins TBTC and TBTO that activated the retinoic acid / X receptor (RAR / RXR) signaling pathway, and (ii) without structural similarities, such as As2O3, DBTC, diazinon, MeHg, ochratoxin A, S9 treated ochratoxin A, S9 treated cyclophosphamide, and S9 treated benzo[a]pyrene, that activated unfolded protein response, and FTY720, lindane, and propanil, that activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the down regulation of acute phase response genes by ochratoxin A. These findings were validated by quantitative Real-Time PCR (Q-RT-PCR) analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene can be used to screen compounds for direct immunotoxicity.
Publication Title
Toxicogenomics-based identification of mechanisms for direct immunotoxicity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 256 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre)frail older adults. Additionally, we examine the effect of resistancetype exercise training on the muscle transcriptome in healthy older subjects and (pre)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Followup samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistancetype exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r=0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistancetype exercise training. Some agerelated changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistancetype exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and reinnervation in ageing muscle.
Publication Title
Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Drosophila melanogaster
- 216 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Many studies have addressed the effects of adult diet on gene expression in Drosophila melanogaster, however, little is known about how developmental diet influences adult gene expression, and how this interacts with adult dietary conditions.
Publication Title
Relating past and present diet to phenotypic and transcriptomic variation in the fruit fly.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 151 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown.
Publication Title
Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Molecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases.
Publication Title
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells (PBMCs) towards a high MUFA or SFA challenge between subjects with different cardiovascular disease risk profiles and to identify fatty-acid specific gene-expression pathways.
Publication Title
High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 128 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health
Publication Title
Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial.
Sample Metadata Fields
Treatment, Subject
View Samples