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GSE11115
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
In addition to their role in the development and function of the reproductive system, estrogens have significant anti-inflammatory properties. Although both estrogen receptors (ERs) can mediate anti-inflammatory actions, ERbeta is a more desirable therapeutic target because ERalpha mediates the proliferative effects of estrogens on the mammary gland and uterus. In fact, selective ERbeta agonists have beneficial effects in preclinical models involving inflammation without causing growth-promoting effects on the uterus or mammary gland. However, their mechanism of action is unclear. The purpose of this study was to use microarray analysis to determine whether ERbeta-selective compounds produce their anti-inflammatory effects by repressing transcription of proinflammatory genes. We identified 49 genes that were activated by TNF-alpha in human osteosarcoma U2OS cells expressing ERbeta. Estradiol treatment significantly reduced the activation by TNF-alpha on 18 genes via ERbeta or ERalpha. Most repressed genes were inflammatory genes, such as TNF-alpha, IL-6, and CSF2. Three ERbeta-selective compounds, ERB-041, WAY-202196, and WAY-214156, repressed the expression of these and other inflammatory genes. ERB-041 was the most ERbeta-selective compound, whereas WAY-202196 and WAY-214156 were the most potent. The ERbeta-selective compounds repressed inflammatory genes by recruiting the coactivator, SRC-2. ERB-041 also repressed cytokine genes in PBMCs, demonstrating that ERbeta-selective estrogens have anti-inflammatory properties in immune cells. Our study suggests that the anti-inflammatory effects of ERB-041 and other ERbeta-selective estrogens in animal models are due to transcriptional repression of proinflammatory genes. These compounds might represent a new class of drugs to treat inflammatory disorders.
Publication Title
Selective estrogen receptor-beta agonists repress transcription of proinflammatory genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 M) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis.
Publication Title
Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better understand the molecular basis of the anticancer effects of acyclic retinoid (ACR), a genome-wide screening was applied to identify novel targets of ACR in human hepatocellular carcinoma (HCC) cells JHH7. Gene expression profiles of JHH7 were measured at 0h, 1h and 4 hours after treatment with1 M All-trans retinoic acid (AtRA) or 10 M ACR. Hierarchical clustering with Wards method of 44,907 genes demonstrated diverse expression changes in HCC cells treated with ACR for 4h. A total of 973 differentially expressed genes in response to ACR by comparing with AtRA for 4h treatments were identified with a fold change more than 2. Then, network analysis was performed on the altered gene expression profiles using Ingenuity Pathways Analysis (IPA) program. The most highly populated networks were associated with the regulation of cell cycle and DNA replication, as ACR is well known to induce apoptosis and suppress cell proliferation in HCC cells. Moreover, networks related with amino acid metabolism, protein synthesis and lipid metabolism, such as the biological network entitled Lipid Metabolism, Small Molecular Biochemistry, Vitamin and Mineral Metabolism were also observed. Of interest, this network contains genes that play critical roles in controlling the development of tissues and organs such as the nuclear orphan receptor nuclear receptor subfamily 2, group F, member 2 (NR2F2), suggesting potential drug targets to prevent/treat HCC.
Publication Title
Metabolome Analyses Uncovered a Novel Inhibitory Effect of Acyclic Retinoid on Aberrant Lipogenesis in a Mouse Diethylnitrosamine-Induced Hepatic Tumorigenesis Model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
6-8 week old BL6, FVB/N and SV129 mouse strains were kept in normoxia or hypobaric hypoxia for 4 weeks and then phenotyped by echocardiogram and right ventricular heart catheterization, followed by tissue collection. In addition, Affymetrix expression analysis was conducted in a paired fashion.
Publication Title
Murine pulmonary response to chronic hypoxia is strain specific.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression of Ethanol-treated hepatocytes from WT and transglutaminase 2 knockout mice
Publication Title
Role of transglutaminase 2 in liver injury via cross-linking and silencing of transcription factor Sp1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
IlluminaHiSeq2500
Description
Va24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer, represent promising therapeutic target. However, reduced iNKT-cell numbers and function have been observed in many patients with cancer. To overcome this obstacle, we reprogramed human iNKT cells to pluripotency and then redifferentiated into regenerated iNKT cells in vitro through IL-7/IL-15-based optimized cytokine combination. They showed proliferation and IFN-? production in response to a-galactosylceramide, induced dendritic cell maturation and downstream activation of cancer antigen-specific cytotoxic T lymphocytes in vitro, and exhibited NKG2D- and DNAM-1-mediated natural killer celllike cytotoxicity against cancer cell lines. Their immunological features and availability in an unlimited supply from induced pluripotent stem cells offer the potential to develop effective immunotherapies against cancer. Overall design: Expression profile of the lymphocytes (n = 17) by highthrouput sequencing
Publication Title
Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-B signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here, we report novel mechanisms of HCC progression through Sharpin overexpression. Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in stably Sharpin-expressing cells. Versican expression increased in the majority of HCC tissues and knocking down of versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of versican transcription synergistically with Wnt/-catenin pathway activation. Furthermore, Sharpin overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes versican expression synergistically with the Wnt/-catenin pathway, potentially contributing to HCC development. A Sharpin/versican axis could be an attractive therapeutic target for this currently untreatable cancer.
Publication Title
Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In embryonic stem cells (ESCs), the expression of development-related genes, including germ cellrelated genes, is globally repressed. The transcription factor MAX represses germ cellrelated gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cellrelated gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cellrelated gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cellrelated genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cellrelated genes in ESCs.
Publication Title
DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
Effect of high fat diet feeding on gene expression
Publication Title
Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The cytokine interleukin-12 (IL-12) is known to play a central role in adaptive and innate immunity.
Publication Title
Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii.
Sample Metadata Fields
Sex
View Samples