Filters
Technology
Platform
GSE42771
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2, ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice.
Publication Title
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway.
Publication Title
Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Raf kinase inhibitor protein (RKIP) is a dual inhibitor of the Raf kinase and the G-protein-coupled receptor kinase 2 (GRK2). GRK2 is an indispensable kinase, which exerts a major role in the pathogenesis of heart failure, and inhibition of GRK2 is cardioprotective in experimental models of heart failure. To investigate the cardiac function of RKIP as GRK2 inhibitor, we generated transgenic mice with myocardium-specific expression of RKIP under control of the alpha-MHC promoter. For comparison, mice with myocardium-specific expression of a GRK-specific peptide inhibitor (GRK-Inh) were also generated. Two different transgenic mouse models were established. Transgenic RKIP mice and transgenic GRK-Inh mice were born at Mendelian frequencey and grew to adulthood normally.
Publication Title
Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hypercholesterolemic APOE-deficient mice are a widely used experimental model of atherosclerosis and increased generation of reactive oxygen species (ROS) is a prominent feature of atherosclerosis development. To study the impact of ROS on atherogenesis, we treated APOE-deficient mice for 7 months with the antioxidant vitamin E (2000 IU/kg diet) and performed whole genome microarray gene expression profiling of aortic genes. Microarray gene expression profiling was performed of whole aortas isolated from vitamin E-treated APOE-deficient relative to untreated APOE-deficient mice with overt atherosclerosis, and nontransgenic B6 control mice. Microarray gene expression profiling revealed that vitamin E treatment prevented atherosclerosis-related gene expression changes of the aortic intima and media.
Publication Title
Microarray gene expression profiling reveals antioxidant-like effects of angiotensin II inhibition in atherosclerosis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The fatty acid synthase (FASN) is the major fat synthesizing enzyme. FASN is an indispensable enzyme because mice with genetic deletion of Fasn are not viable. Apart from its physiological function, previous studies indicated that FASN could also exert a pathophysiological role, in the heart, because patients with heart failure showed up-reguation of FASN. To investigate the in vivo function of FASN up-regulation in the heart, we generated mice with myocardium-specific expression of FASN under control of the alpha-MHC promoter. Two different founder lines were generated with high and low FASN over-expression. Microarray gene expression profiling of heart tissue was performed of heart tissue from transgenic mice with high and low FASN expression
Publication Title
Inhibition of G-protein-coupled Receptor Kinase 2 Prevents the Dysfunctional Cardiac Substrate Metabolism in Fatty Acid Synthase Transgenic Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling of human embryonic kidney (HEK293) cells was performed to determine the effect of high and low glucose on gene expression. Microarrays were used to identify distinct classes of genes up-regulated in HEK293 cells during cultivation for 7 days in medium with physiological (low) glucose compared to high glucose.
Publication Title
Calreticulin enhances B2 bradykinin receptor maturation and heterodimerization.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We established a novel model to assess the function of proteins under in vivo conditions. The model relies on the expansion of HEK293 cells in immunodeficient NOD.Scid mice. To validate the novel model, we performed microarray gene expression profiling of NOD.Scid-expanded HEK293 cells relative to conventionally cultivated cells. Microarray analysis revealed that cell expansion in NOD.Scid mice restored an imbalanced chaperone system without inducing a major upregulation of the entire protein folding machinery.
Publication Title
Establishment of an in vivo model facilitates B2 receptor protein maturation and heterodimerization.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray gene expression profiling of aorta genes of APOE-deficient mice receiving atherosclerosis treatment with the ACE inhibitor captopril.
Publication Title
Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
Description
Cancer evolution is fueled by genetic and epigenetic diversity, and intra-tumoral heterogeneity in DNA methylation has been shown to co-operate with genetic heterogeneity to empower evolutionary capacity of cancers such as chronic lymphocytic leukemia. Here, we show that epigenetic diversification leads to decreased coordination across layers of epigenetic information, likely reflecting an admixture of cells with diverging epigenetic identities. This manifests in incomplete gene silencing by the Polycomb complex, unexpected co-occurrence of typically mutually exclusive activating and repressing histone modifications, and greater cell-to-cell transcriptional heterogeneity. Overall design: Given the importance of histone modifications to lineage plasticity in cancer15-17, intra-leukemic epigenetic heterogeneity may extend to histone modifications, likely promoting lineage plasticity by enabling permissive chromatin states. To address this question, we complemented DNAme analysis with a chromatin immunoprecipitation sequencing (ChIP-seq) compendium of histone post-translational modifications (H3K4me3, H3K27ac, H3K4me1, H3K27me3, H3K9me3 and H3K36me3) and transcriptome sequencing (RNA-seq) in a cohort of primary CLL and healthy B lymphocytes samples (CLL IGHV unmutated, n = 12; CLL IGHV mutated, n = 10; peripheral blood NBCs [CD23+CD19+CD27-IgD+], peripheral blood memory B cells [GCBs; CD23+CD19+CD27+IgD-], peripheral blood CD20+ cells.
Publication Title
Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- IlluminaHiSeq2000
Description
Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. Overall design: mRNA profiling in bone marrow mononuclear cells (BM MNC) from 14 CMML patients (8 decitabine responders vs. 6 non-responders).
Publication Title
Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples