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GSE157754
Mus musculus
3 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study we investigate the role of IL-4 receptor a subunit in intestinal inflammation using DSS-induced colitis model. Our finding suggest that IL-4Ra deficiency enhances intestinal mucosal barrier function through the upregulation of NOX1-dependent ROS production, thereby suppressing the development of intestinal inflammation.
Publication Title
Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Shikonin is a active component isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon and exhibits multiple pharmacological properties, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. Here, the effects of shikonin on the gene expression of human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with 100 nM shikonin, and followed by incubation for 3h at 37C. Flow cytometry analysis with Annexin-V and propidium iodide demonstrated that no cell death was observed in the cells at 100 nM shikonin. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with the compound.
Publication Title
Chemical inducers of heat shock proteins derived from medicinal plants and cytoprotective genes response.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
White adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
Publication Title
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
White adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gs- and Gi-coupled receptors have been reported to regulate lipolysis, and Gq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of G12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates G12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed metabolically healthy obese phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
Publication Title
The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The arylhydrocarbon receptor is a ligand inducible transcription factor. Known to control xenobiotic metabolizing enzymes, it also affects - depending on the cell type - numerous other genes, either directly or indirectly. With respect to the immune system, persistent activation leads to immunosuppression. We asked how the AhR is involved in Langerhans cells. These antigen presenting cells of the skin are responsible for allergies against chemicals (thus xenobiotic metabolism might be relevant) and a recently detected endogenous ligand, FICZ made by UVB radiation from tryptophane, is particularly abundant in the skin.
Publication Title
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The transcriptome of murine LC after 24 hours in vivo exposure to a moderate dose of 10 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied.
Publication Title
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
Illumina HiSeq 2500
Description
Treatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor’s gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2''-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. Overall design: The transcriptomes, proteomes and HLA peptidomes of the U-87, T98G and LNT-229 GBM human cell lines were analyzed before and after treatment with Decitabine. Overall, the RNA-Seq transcriptome analyses resulted in the identification of above 26000 transcripts, the proteome analyses identified about 7500 proteins and the HLA class I peptidome analyses resulted in above 25000 identified HLA peptides. Two biological repetitions of the transcriptome, three of the proteome and three of the HLA peptidome were performed with each of the cell lines and treatment, resulting in highly reproducible datasets.
Publication Title
Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations within the catalytic domain of the histone methyltransferase (HMT) EZH2 have been identified in subsets of Non-Hodgkin Lymphoma (NHL) patients. These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We previously reported the discovery of a potent, selective, S-adenosyl-methionine-competitive and orally bioavailable small molecule inhibitor of EZH2, EPZ-6438. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) led to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent tumor growth inhibition and eradication of genetically altered NHL with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 day after stopping compound treatment in two EZH2 mutant xenograft models. These data confirm the dependency of mutant NHL on EZH2 activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.
Publication Title
Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secreted proteins, termed hepatokines.
Publication Title
A liver-derived secretory protein, selenoprotein P, causes insulin resistance.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples