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GSE18614
Mus musculus
27 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States. 3-Hydroxyacetanilide (AMAP), a regioisomer of acetaminophen is useful as a comparative tool for studying APAP-induced toxicity since it is non-toxic relative to APAP. TGF-alpha transgenic mouse hepatocytes were treated with both isomers to investigate mitogen-activated protein kinase cascades in order to differentiate their toxicological outcomes. Mitogen-activated protein kinase (MAPK) cascade expression and activation were measured using microarray and Bioplex technologies, respectively. APAP treatment led to c-Jun N-terminal kinase (JNK) activation, whereas AMAP treatment led to the activation of extracellular-signal-regulated protein kinase (ERK). The microarray data suggested APAP treatment may upregulate gene expression at multiple levels of the JNK cascade including a JNK-related scaffold protein. Expression data was related to phosphoprotein levels using the Bioplex system. APAP treatment led to a significant activation of JNK compared to its regioisomer. In contrast, microarray analysis of AMAP showed a slight upregulation of ERK gene activity. Furthermore, Bioplex data showed AMAP treatment led to significant ERK phosphorylation compared to APAP. Cell viability assays confirmed that APAP-induced activation of JNK was related to higher rates of cell death, whereas activation of ERK by AMAP may be cytoprotective.
Publication Title
Differential regulation of mitogen-activated protein kinase pathways by acetaminophen and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide in TAMH cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 248 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Craniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of isolated single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive at best. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as potential genetic biomarkers for single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Furthermore, pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only differentially regulated genes identified in a direct comparison. These results not only confirm the roles of previously reported craniosynostosis-related targets but also introduce novel genetic biomarkers and pathways that may play critical roles in its pathogenesis.
Publication Title
Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of the present study was to compare hepatic toxicogenomic signatures across in vitro and in vivo mouse models following exposure to acetaminophen (APAP) or its relatively nontoxic regioisomer 3'-hydroxyacetanilide (AMAP). Two different Affymetrix microarray platforms and one Agilent Oligonucleotide microarray were utilized. APAP and AMAP treatments resulted in significant and large changes in gene expression that were quite disparate, and likely related to their different toxicologic profiles. Ten transcripts, all of which have been implicated in p53 signaling, were identified as differentially regulated at all time-points following APAP and AMAP treatments across multiple microarray platforms. Protein-level quantification of p53 activity aligned with results from the transcriptomic analysis, thus supporting the implicated mechanism of APAP-induced toxicity. Therefore, the results of this study provide good evidence that APAP-induced p53 phosphorylation and an altered p53-driven transcriptional response are fundamental steps in APAP-induced toxicity.
Publication Title
p53 Contributes to Differentiating Gene Expression Following Exposure to Acetaminophen and Its Less Hepatotoxic Regioisomer Both In Vitro and In Vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Epidemiologic and animal studies implicate overconsumption of fructose in the development of non-alcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remains largely unknown. We present evidence supporting the essential function of the lipogenic transcription factor ChREBP in mediating adaptation response to fructose and protecting against fructose-induced hepatotoxicity. High-fructose diet (HFrD) activates hepatic lipogenesis via a ChREBP-dependent manner in wildtype mice, while inducing steatohepatitis in Chrebp-KO mice. In Chrebp-KO mouse livers, HFrD reduces levels of molecular chaperones and activates the CHOP-dependent unfolded protein response, whereas administration of chemical chaperone or Chop shRNA rescues liver injury. Gene expression profiling revealed elevated expression of cholesterol biosynthesis genes in Chrebp-KO livers after HFrD, in parallel with increased abundance of nuclear SREBP2.
Publication Title
Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
- Gene expression changes linked to two step immortalization of human mammary epithelial cells (HMEC).
Publication Title
A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Ion Torrent Proton
Description
The TNF family member TL1A (TNFSF15) co-stimulates several T helper subsets and promotes T cell-dependent models of inflammatory diseases, including inflammatory bowel diseases (IBD) and allergic lung disease. TL1A polymorphisms confer susceptibility to IBD and have been associated with disease severity. In this study, we identified TL1A as a strong inducer of TH9 cell differentiation in vitro. Mechanistically, TL1A induced NF-?B signaling and down-stream STAT6 activation and facilitated cooperative binding of BATF, BATF3, and IRF4 to the Il9 promoter. In vivo, utilizing an adoptive T cell transfer model we demonstrated that TL1A promoted IL-9-dependent, TH9 cell-induced intestinal and lung inflammation and blocking anti-IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role for IL-9 in TL1A-induced mucosal inflammation. Overall design: 4 samples (2x2)
Publication Title
A role for BATF3 in T<sub>H</sub>9 differentiation and T-cell-driven mucosal pathologies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
These gene expression microarrays were performed as part of a project aiming to integrate quantitative proteomic, gene expression and epigenetic data from the childhood brain tumor medulloblastoma.
Publication Title
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays were used to detail the global program of gene expression underlying differences in the organisation of inflammatory cells classified by the expression of the CD21L and IL-17A genes. Synovia were defined by the expression of the CD21L and IL-17A genes as determined by semi-quantitative PCR.
Publication Title
Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparing Platforms for Messenger RNA Expression Profiling of Archival Formalin-Fixed, Paraffin-Embedded Tissues.
Sample Metadata Fields
Specimen part, Disease
View Samples