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GSE93798
Homo sapiens
39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN.
Publication Title
Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The aim of this study was to identify genes regulated by IL-12, IL-18 and IFN-alpha during early differentiation of human Th1 cells
Publication Title
Activating transcription factor 3 is a positive regulator of human IFNG gene expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
Illumina HiSeq 2500
Description
One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-ß (Aß) peptide. ApoE influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aß in the brain. In addition to influencing Aß metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1?E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aß morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology. Overall design: Assessed the cortical gene expression of 6-month old APPPS1-21;ApoE-/- (n=7) and APPPS1-21 mice (n=6).
Publication Title
ApoE facilitates the microglial response to amyloid plaque pathology.
Sample Metadata Fields
Cell line, Subject
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
RNAseq analysis of cloche m39 mutant zebrafish embryos and wild type siblings at 90% epiboly - tailbud stage Overall design: In order to isolate the cloche gene, RNAseq was performed on a deletion allele of the zebrafish cloche mutant. RNA was extracted from individual embryos at a stage the cloche gene was predicted to be expressed based on previous literature. RNA from the respective genoptypes was then pooled and subjected to RNAseq analysis.
Publication Title
Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Human cardiomyopathies often lead to heart failure, a major cause of morbidity and mortality in industrialized nations. Described here is a phenotypic characterization of cardiac function and genome-wide expression from C3H/HeJ, C57BL/6J, and B6C3F1/J male mice. Histopathologic analysis identified a low-grade background cardiomyopathy (murine progressive cardiomyopathy) in eight of nine male C3H/HeJ mice (age nine to ten weeks), but not in male C57BL/6J and in only of ten male B6C3F1/J mice. The C3H/HeJ mouse had an increased heart rate and a shorter RR interval compared to the B6C3F1/J and C57BL/6J mice. Cardiac genomic studies indicated the B6C3F1/J mice exhibited an intermediate gene expression phenotype relative to the 2 parental strains. Disease-centric enrichment analysis indicated a number of cardiomyopathy-associated genes were induced in B6C3F1/J and C3H/HeJ mice, including Myh7, My14, and Lmna and also indicated differential expression of genes associated with metabolic (e.g., Pdk2) and hypoxic stress (e.g. Hif1a). A novel coexpression and integrated pathway network analysis indicated Prkaa2, Pdk2, Rhoj, and Sgcb are likely to play a central role in the pathophysiology of murine progressive cardiomyopathy in C3H/HeJ mice. Our studies indicate that genetically determined baseline differences in cardiac phenotype have the potential to influence the results of cardiotoxicity studies.
Publication Title
Comparative phenotypic assessment of cardiac pathology, physiology, and gene expression in C3H/HeJ, C57BL/6J, and B6C3F1/J mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Early during culture of primary mouse HSCs gene expression changes.
Publication Title
Gene expression profiling of early hepatic stellate cell activation reveals a role for Igfbp3 in cell migration.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this question, healthy male WKY rats (12 wks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 ug/m3 of aerosolized Zn in sulfate form, 5 h/d, 3 d/wk for 16 wks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl ?-D-glucosaminidase, ?-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels may induce cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.
Publication Title
Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ginkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement for various indications such as improving neural function, anti-oxidant and anti-cancer effects. As part of the herbal supplement industry, these compounds are largely unregulated, and may be consumed in large concentrations over extended periods of time. This is of particular concern, because the long-term effects in terms of toxicity and carcinogenicity data is lacking for many herbal products, including GBE. The 2-year B6C3F1 mouse carcinogenicity bioassay indicated a marked dose-related increase in hepatocellular carcinoma (HCC) development associated with exposure to GBE. We have shown that the mechanism of this increase in tumorigenesis is related to a marked increase in the incidence of -catenin mutation, and report a novel mechanism of constitutive -catenin activation through post-translational modification leading to constitutive Wnt signaling and unregulated growth signaling and oncogenesis. Furthermore, using global gene expression profiling, we show that GBE-induced HCC exhibit overrepresentation of gene categories associated with human cancer and HCC signaling including upregulation of relevant oncogenes and suppression of critical tumor suppressor genes, as well as chronic oxidative stress, a known inducer of calpain-mediated degradation and promoter of hepatocarcinogenesis in humans. These data provide a molecular mechanism to GBE-induced HCC in B6C3F1 mice that is relevant to human cancer, and provides relevant molecular data that will provide the groundwork for further risk assessment of unregulated compounds, including herbal supplements.
Publication Title
Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.)
Publication Title
One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples