Modulation of the transcriptional response to recombinant IFN-β by Acetaminophen
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Aaron Farnsworth
PROVIDER: E-GEOD-18949 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2010-12-09 | E-GEOD-19437 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE24907: Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (gene expression) GSE24909: Lack of hepatic response of microRNA in mice following chronic benzo(a)pyrene exposure (miRNA) Refer to individual Series
2011-10-18 | E-GEOD-24910 | biostudies-arrayexpress
Project description:Adult male mice were exposed to 150 mg/kg benzo(a)pyrene (BaP) or solvent for 3 days and sampled 4 or 24 hours after the last dose. mRNA expression levels in adult mouse liver were measured using Agilent arrays. We found widespread changes in mRNA in pathways consistent with known response (xenobiotic metabolism, glutathione). We also found that BaP caused changes in the circadian rhythm pathway. We measured miRNA changes in the same samples and found no evidence for any change in transcription of miRNA as a result of the exposure. Keywords: Toxicology, time course Adult male B6C3F1 mice were exposed to a daily dose of corn oil (vehicle control group) or 150 mg/kg BaP (treatment group) for 3 days (n=5 per group). Mice were sacrificed at 4 h or 24 h following the last dose and liver lobes were extracted and flash frozen. RNA was extracted from median liver lobes and hybridized to the Agilent 4 x 44K mouse DNA arrays using a randomized block design.
2010-10-18 | E-GEOD-18789 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.
2010-08-20 | E-GEOD-21277 | biostudies-arrayexpress
Project description:Benzo[a]pyrene (BaP) is a very extensively studied prototypical polycyclic aromatic hydrocarbons (PAHs). Previous work in our laboratory showed no changes of microRNA (miRNA) expression in liver following a 3 days exposure to BaP, suggesting a lack of miRNA transcriptional responses to aryl hydrocarbon receptor agonists and/or DNA damage. Here, we studied 25-week old male MutaTM Mouse exposed to 25, 50, and 75 mg/kg/day BaP by oral gavage for 28 consecutive days. MAANOVA identified 110 differentially expressed genes (adjusted p < 0.05) with fold change greater than 1.5. The genes most affected included those involved in xenobiotic metabolism, phase II metabolizing enzymes, as well as the downstream targets of p53. Pathway specific RT-PCR was used to confirm the p53 response. A single significant increase in miRNA expression was identified (mir-34a and validated using the Qiagen miScript PCR system). This miRNA is known to be transcriptionally activated by p53. Ingestion of BaP leads to widespread changes in gene expression in mouse liver, with enrichment of genes involved in cell cycle arrest, DNA damage response, and apoptosis via the p53 pathway. In contrast, miRNA expression was relatively unaffected. Only miR-34a was significantly up-regulated, and may therefore play a critical role in the post-transcriptional regulation of p53 and/or its downstream targets. Keywords: Agilent mouse 4 x 44 oligonucleotide microarrays were used to assess global gene expression in response to 25, 50, and 75 mg/kg BaP treatment Individual total RNA (200 ng) from 5 mice per treatment group (control, 24mg/kg, 50mg/kg, and 75mg/kg) and universal reference total RNA (Stratagene, Mississauga, ON, Canada) was used to synthesize double stranded cDNA.
2011-10-18 | E-GEOD-24907 | biostudies-arrayexpress
Project description:Polycyclic aromatic hydrocarbons (PAHs) are widely distributed, carcinogenic environmental contaminants produced as a consequence of the incomplete combustion of fossil fuels. Benzo[a]pyrene (BaP) is a very extensively studied prototypical PAH. We recently reported a complete lack of change in microRNA (miRNA) expression in adult mouse liver following oral gavage with BaP despite a robust transcriptome response. We hypothesized that hepatic miRNAs may not be highly responsive to the treatment. Here, we analyse the pulmonary mRNA and miRNA response to BaP in the same mice. Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Acute exposure to BaP resulted in modest decreases in serum inorganic phosphorous, calcium, glucose, alkaline phosphatase and lactate dehydrogenase in animals treated with 300 mg/kg BaP. 32P postlabeling of DNA revealed similar increases in BaP-DNA adducts in both lungs and livers of exposed mice in a dose dependent manner at the 4 hour time point. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. Over 1,000 genes were statistically differentially expressed (fold change > 1.5 and p < 0.05), encompassing numerous pathways including: oxidative stress, xenobiotic metabolism, cell proliferation, cell cycle, B and T-cell receptor signalling and primary immunodeficiency signalling pathways. Analysis of miRNA profiles revealed downregulation of miR-150, miR-142-5p, 142-3p and upregulation of miR-34c and miR-29b. These miRNAs are involved in various biological processes including immune response, cell proliferation and cell cycle, which are also the main pathways affected at the gene expression level. As BaP exposure does not result in hepatocarcinogenicity, but does cause lung cancer, these miRNAs may play an important role in the outcome of the exposure and be more predictive of carcinogenesis. Keywords: mRNA, miRNA, Pulmonary, non-target tissue, Toxicogenomics, Benzoapyrene Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. This submission only contains the 4hr time point, at control, 150mg/kg and 300mg/kg (except for the liver study where only the control and 300mg/kg samples were used).
2011-10-03 | E-GEOD-24751 | biostudies-arrayexpress