Filters
Technology
Platform
GSE9951
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND: Cadmium is implicated in prostate carcinogenesis, but its oncogenic action remains unclear.
Publication Title
Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 1000
Description
Carbon nanotubes (CNTs) are fibrous particulates made up of elemental carbon and a novel nanomaterial known for its variety of industrial applications. It has been shown that lung exposure to CNTs may cause adverse effects inclunding lung inflammation and remodeling in experimental models. We investigated the impact of genetic background on the development of adverse outcomes by comparing several common inbred mouse strains and found that C57Bl/6 and DBA/2 strains were polarized in their sensitivity to adverse changes at 4 weeks following an exposure to 4 mg/kg CNT. Here we compare underlying gene expression profiles which may inform the understanding of lung biology underpinning genetic susceptibility to adverse outcomes following environmental or occupational exposure to CNTs. Overall design: Changes in mRNA profiles were compared between CNT-exposed animals and vehicle-treated controls (n=3/group) of either C57Bl/6 or DBA/2 strains.
Publication Title
Genetic susceptibility to toxicologic lung responses among inbred mouse strains following exposure to carbon nanotubes and profiling of underlying gene networks.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, and subject to disruption by exposure to environmental agents such as hexavalent chromium. Cr(VI) exposure can cause chromosomal disruption through formation of Cr-DNA adducts, free radical-induced DNA damage, and DNA-Cr-protein and DNA-Cr-DNA cross-links, all of which may disrupt chromatin remodeling mechanisms responsible for maintenance or controlled modification of epigenetic homeostasis. In addition, dose-response analyses have shown that acute exposures to high-concentrations of Cr(VI) and chronic exposures to low-concentrations of the same agent lead to significantly different transcriptomic and genomic stability outcomes. To investigate how transcriptional responses to chromium exposure might correlate to structural changes in chromatin, we have used whole genome Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis coupled with deep sequencing to identify regions of the genome that switch from open to closed chromatin or vice versa in response to exposure to varying Cr(VI) concentrations. We find that the switch affects gene expression levels in the target areas that vary depending on Cr(VI) concentration. At either Cr(VI) concentration, chromatin domains surrounding binding sites for AP-1 transcription factors become significantly open, treatment whereas BACH2 and CTCF binding sites are open solely at the low and high concentrations, respectively. Our results suggest that FAIRE may be a useful technique to map chromatin elements targeted by DNA damaging agents for which there is no prior knowledge of their specificity, and to identify subsequent transcriptomic changes induced by those agents. Overall design: Cr25 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq. Cr0.5 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq.
Publication Title
Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 344 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome analysis of MCF-7 cells exposed for 48 hours to various concentrations of xenoestrogen chemicals.
Publication Title
Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 1000
Description
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene-environment interactions. In addition, many AHR target genes that have been identified by genome-wide profiling have morphogenetic functions, suggesting that AHR activation may play a role in embryonic development. To address this hypothesis, we studied the consequences of AHR activation by TCDD, its prototypical ligand, during spontaneous mouse ES cell differentiation into contractile cardiomyocytes. Treatment with TCDD or shRNA-mediated AHR knockdown significantly decreased the ability of cardiomyocytes to contract and the expression of cardiac markers in these cells. An AHR-positive embryonic stem cell lineage was generated that expressed puromycin resistance and eGFP under the control of the AHR-responsive Cyp1a1 promoter. Cells of this lineage were over 90% pure and expressed AHR as well as cardiomyocyte markers. Analysis of temporal trajectories of global gene expression in these cells shows that activation of the AHR/TCDD axis disrupts the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and Trithorax Group genes. More than 50% of the homeobox factors so regulated do not have AhRE sites in their promoters, indicating that AHR activation may establish a complex regulatory network that reaches beyond direct AHR signaling and is capable of disrupting various aspects of embryonic development, including cardiomyocyte differentiation. Overall design: mRNA profiles of WT and selected AHR positive cells at different differentiation days treated with and without TCDD in duplicates
Publication Title
Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
G-1 is an agonist to GPR30. Activation of GPR30 by G-1 inhibited prostate cancer cell growth in LNCaP xenografts regrown after catration of the host (nude mice), but not in the androgen-sensitive LNCaP xenograft grown in an intact host. Results provide insights into the molecular basis of G-1 action in castration-resistant prostate cancer.
Publication Title
Targeting GPR30 with G-1: a new therapeutic target for castration-resistant prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1000
Description
Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of stromal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent animals models generated in our lab demonstrate clinical phenotypes seen in human fibrotic disease. The mouse model of transforming growth factor-a (TGFa)-induced fibrosis include conditionally expressing TGFa in the lung epithelium under control of the CCSP promoter driving rtTA expression (CCSP/TGFa). This allow the TGFa is only expressed in airway and alveolar epithelial cells and only when mice fed doxycycline (Dox). Similar to PF in humans, TGFa mice on Dox developed a progressive and extensive adventitial, interstitial and pleural fibrosis with a decline in lung mechanics. Thus, the TGFa transgenic mouse is a powerful model to determine lung cell-specific molecular signatures involved in pulmonary fibrosis. In this study, we sought to determine changes in the transcriptome during TGFa-induced pulmonary fibrosis. Our results showed that several pro-fibrotic genes increased in the lungs of TGFa mice. This study demonstrates that WT1 network gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a critical regulator fibrotic lung disease. Overall design: mRNA profiles of CCSP/- and CCSP/TGFalpha mice treated with Dox
Publication Title
Fibrocytes Regulate Wilms Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 1000
Description
Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR). ADMA levels in bronchoalveolar lavage fluid (BALF) and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM). Airway inflammation was assessed by bronchoalveolar lavage (BAL) total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS) signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses. Overall design: mRNA profiles of WT and DDAH1-transgenic mice treated with PBS or house dust mite (HDM).
Publication Title
Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1000
Description
Interleukin-31 (IL-31), a T cells derived cytokine which is mainly produced by CD4+ T cells skewed towards Th2 phenotypes. It signals via a heterodimeric receptors composed of IL-31RA and OSMR that is expressed constitutively in epithelial cells and keratinocytes. IL-31 is shown to play a pathogenic role in allergic and inflammatory diseases. Transgenic mice overexpressing IL-31 have a phenotype similar to atopic dermatitis. Here, we studied the role of IL-31 in skin damage by intradermal administration of recombinant IL-31. Notably, IL-31 was sufficient to increase epidermal basal cell proliferation and thickening of the epidermal layer of skin in mice. Analysis of skin transcriptome indicates a significant increase in the transcripts involved in epidermal cell proliferation and pathological skin remodeling. Thus, our study revealed an important role of IL-31 signaling in activating transcriptional programs involved in the pathophysiology of skin diseases. Overall design: mRNA profiles of C57BL/6 mice skin injected with saline and rIL-31 (20µg) via i.d.
Publication Title
IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 1000
Description
Pulmonary fibrosis is often triggered by an epithelial injury resulting in the formation of fibrotic lesions in the lung, which progress to impair gas exchange and ultimately cause death. Recent clinical trials using drugs that target either inflammation or a specific molecule have failed, suggesting that multiple pathways and cellular processes need to be attenuated for effective reversal of established and progressive fibrosis. Although activation of MAPK and PI3K pathways have been detected in human fibrotic lung samples, the therapeutic benefits of in vivo modulation of the MAPK and PI3K pathways in combination are unknown. Overexpression of TGFa in the lung epithelium of transgenic mice results in the formation of fibrotic lesions similar to those found in human pulmonary fibrosis, and previous work from our group shows that inhibitors of either the MAPK or PI3K pathway can alter the progression of fibrosis. In this study, we sought to determine whether simultaneous inhibition of the MAPK and PI3K signaling pathways is a more effective therapeutic strategy for established and progressive pulmonary fibrosis. Our results showed that inhibiting both pathways had additive effects compared to inhibiting either pathway alone in reducing fibrotic burden, including reducing lung weight, pleural thickness, and total collagen in the lungs of TGFa mice. This study demonstrates that inhibiting MEK and PI3K in combination abolishes proliferative gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a therapeutic option in the treatment of human fibrotic lung disease where these pathways play a role. Overall design: mRNA profiles of CCSP/TGFalpha mice treated with vehicle, ARRY, PX-866, ARRY/PX-866
Publication Title
Dual targeting of MEK and PI3K pathways attenuates established and progressive pulmonary fibrosis.
Sample Metadata Fields
No sample metadata fields
View Samples