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GSE80633
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify gene expression changes associated with Crtc1 deficiency, we performed genome-wide transcriptome profile analyses by using mouse cDNA microarrays in the cortex of Crtc1/ and WT female mice
Publication Title
Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.
Publication Title
Molecular clock is involved in predictive circadian adjustment of renal function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Escherichia coli
- 20 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcription termination factor Rho is essential in enterobacteria. We inhibited Rho activity with bicyclomycin and used microarray experiments to assess Rho function on a genome-wide scale. Rho is a global regulator of gene expression that matches E. coli transcription to translational needs. Remarkably, genes that are most repressed by Rho are prophages and other horizontally-acquired portions of the genome. Elimination of these foreign DNA elements increases resistance to bicyclomycin. Although rho remains essential, such reduced-genome bacteria no longer require Rho cofactors NusA and NusG. Thus, Rho termination, supported by NusA and NusG, is required to suppress the toxic activity of foreign DNA.
Publication Title
Termination factor Rho and its cofactors NusA and NusG silence foreign DNA in E. coli.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The success of TNF inhibitors for treatment of psoriasis and other inflammatory diseases was previously attributed to blockade of innate immunity. In a clinical trial using etanercept TNF blocking agent to treat psoriasis vulgaris, we used affymetrix gene arrays to analyze broad gene profiles in lesional skin at multiple timepoints during drug treatment (baseline, and weeks 1, 2, 4 and 12) compared to non-lesional skin. This analysis created a temporal model of TNF-dependent gene regulation that informs molecular mechanisms of TNF-mediated inflammation. We identified four gene clusters that were differentially down-modulated during etanercept treatment: the cluster down-regulated most rapidly contained mostly dendritic cell activation genes. Culturing human keratinocytes with TNF, IFNg and IL-17 generated a list of keratinocyte genes regulated by each cytokine. The IL-17 pathway genes were strongly down-modulated early, whereas IFNg pathway genes were not down-modulated until final disease resolution at week 12. Finally, we show that TNF blockade rapidly inhibits IL-12/IL-23 p40 subunit expression, and that p40 neutralization inhibits psoriatic dermal migr-mediated Th17 polarization. We hypothesize that etanercept inhibits myeloid dendritic cell production of IL-23, a Th17 survival cytokine, resulting in rapid downregulation of IL-17 pathway genes. This data links effects of TNF blockade on the innate immune system with the adaptive immune system.
Publication Title
Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atopic dermatitis (AD) is a common inflammatory skin disease with a T(H)2 and T22 immune polarity. Despite recent data showing a genetic predisposition to epidermal barrier defects in some patients, a fundamental debate still exists regarding the role of barrier abnormalities versus immune responses in initiating the disease. An extensive study of nonlesional AD (ANL) skin is necessary to explore whether there is an intrinsic predisposition to barrier abnormalities, background immune activation, or both in patients with AD. We sought to characterize ANL skin by determining whether epidermal differentiation and immune abnormalities that characterize lesional AD (AL) skin are also reflected in ANL skin. We performed genomic and histologic profiling of both ANL and AL skin lesions (n = 12 each) compared with normal human skin (n = 10). We found that ANL skin is clearly distinct from normal skin with respect to terminal differentiation and some immune abnormalities and that it has a cutaneous expansion of T cells. We also showed that ANL skin has a variable immune phenotype, which is largely determined by disease extent and severity. Whereas broad terminal differentiation abnormalities were largely similar between involved and uninvolved AD skin, perhaps accounting for the background skin phenotype, increased expression of immune-related genes was among the most obvious differences between AL and ANL skin, potentially reflecting the clinical disease phenotype. Our study implies that systemic immune activation might play a role in alteration of the normal epidermal phenotype, as suggested by the high correlation in expression of immune genes in ANL skin with the disease severity index.
Publication Title
Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we used genomic profiling to characterize differences in expression of genes related to epidermal growth/differentiation and inflammatory circuits in skin lesions of psoriasis and atopic dermatitis (AD), comparing expression values to normal skin. Skin biopsies were collected from 9 patients with chronic atopic dermatitis, 15 psoriasis patients, and 9 healthy volunteers.
Publication Title
Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: IL-17 is the defining cytokine of the Th17, Tc17, and T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-, TNF-, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro.
Publication Title
IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The process for making monocyte derived DCs (moDCs) has been previously described (46). All analysis was performed on day 5 immature DCs. Etanercept 10mg/mL was added to experimental wells on days 0, 2, and 4. We chose this concentration of etanercept as it approximates the plasma concentration of drug when given 50mg BIW.
Publication Title
Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mycosis Fungoides (MF) is typically characterized by a mature CD4+ memory T-cell phenotype, and regarded as a helper T-cell (Th)2-skewed disease. Here, using skin samples from MF (n=21), healthy volunteers (n=17), atopic dermatitis (n=17), and psoriasis (n=9), we performed RT-PCR to show highest interleukin (IL)-32 mRNA expression in MF compared to benign inflammatory diseases, and its increasing expression with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression by numerous CD3+CD4+ T-cells and some epidermotropic T-cells in MF lesions. IL-32 is expressed by MyLa cells (MF cell line) and promoted their proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and HH cells (CTCL cell line) showed upregulation of cell proliferation and survival genes. Of major 'polar' T-cell cytokines, only IFN- mRNA increases with MF progression and positively correlates with IL-32 mRNA expression levels. Th2 cytokines do not show consistent increases with MF progression nor positive correlation with IL-32 mRNA expression levels. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individulas was found in IFN-+ and IFN-- cells but not in IL-4+ or IL-13+ cells. In conclusion, we identified IL-32+ cells as likely tumor cells in MF, and clearly showed that IL-32 mRNA expression levels increase with MF progression. We found that IL-32 mRNA expression levels in MF are significantly higher than those in other skin diseases, and that some IL-32+ T-cells are independent from defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine.
Publication Title
IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4R that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail.
Publication Title
Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples