A Time-series transcriptome analysis of Rosiglitazone effects in mice neonatal cardiomyocytes.
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ABSTRACT:
ORGANISM(S): Rattus norvegicus albus
PROVIDER: GSE117198 | GEO | 2020/02/26
REPOSITORIES: GEO
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Project description:Rosiglitazone, a peroxisome proliferator-activated receptor g (PPARg) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone.
2010-06-25 | GSE22553 | GEO
Project description:Here we report, for the first time, the acute effects of the synthetic PPARγ agonist rosiglitazone on the transcriptional network of PPARγ in adipocytes. Treatment with Rosiglitazone for 1 hour leads to acute transcriptional activation as well as repression of a number of genes as determined by genome-wide RNA polymerase II occupancy. Unlike what has been shown for many other nuclear receptors, agonist treatment does not lead to major changes in the occurrence of PPARγ binding sites. However, rosiglitazone promotes PPARγ occupancy at many preexisting sites, and this is paralleled by increased occupancy of the mediator subunit MED1. The increase in PPARγ and MED1 binding is correlated with an increase in transcription of nearby genes indicating that rosiglitazone, in addition to activating the receptor, also promotes its association with DNA, and that this is causally linked to recruitment of mediator and activation of genes. Notably, both Rosiglitazone-activated and -repressed genes are induced during adipogenesis. However, Rosiglitazone-activated genes are markedly more associated with PPARγ than repressed genes and are highly dependent on PPARγ for expression in adipocytes. By contrast, repressed genes are associated with the other key adipocyte transcription factor CCAAT-Enhancer binding protein (C/EBPα), and their expression is more dependent on C/EBPα. This suggests that the relative occupancies of PPARγ and C/EBPα are critical for whether genes will be induced or repressed by PPARγ agonist. Examination of binding of PPARγ, C/EBPα, RNAPII, CBP and MED1 in mature 3T3-L1 adipocytes treated with 1 μM Rosiglitazone and/or 0.1% DMSO for 1 hour.
2013-08-01 | E-GEOD-49423 | biostudies-arrayexpress
Project description:Rosiglitazone, a peroxisome proliferator-activated receptor g (PPARg) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone. Male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone once per day for 14 days. Samples were obtained 6, 24, 168 or 336 hours after the final treatment.
2010-07-29 | E-GEOD-22553 | biostudies-arrayexpress
Project description:Here we report, for the first time, the acute effects of the synthetic PPARγ agonist rosiglitazone on the transcriptional network of PPARγ in adipocytes. Treatment with Rosiglitazone for 1 hour leads to acute transcriptional activation as well as repression of a number of genes as determined by genome-wide RNA polymerase II occupancy. Unlike what has been shown for many other nuclear receptors, agonist treatment does not lead to major changes in the occurrence of PPARγ binding sites. However, rosiglitazone promotes PPARγ occupancy at many preexisting sites, and this is paralleled by increased occupancy of the mediator subunit MED1. The increase in PPARγ and MED1 binding is correlated with an increase in transcription of nearby genes indicating that rosiglitazone, in addition to activating the receptor, also promotes its association with DNA, and that this is causally linked to recruitment of mediator and activation of genes. Notably, both Rosiglitazone-activated and -repressed genes are induced during adipogenesis. However, Rosiglitazone-activated genes are markedly more associated with PPARγ than repressed genes and are highly dependent on PPARγ for expression in adipocytes. By contrast, repressed genes are associated with the other key adipocyte transcription factor CCAAT-Enhancer binding protein (C/EBPα), and their expression is more dependent on C/EBPα. This suggests that the relative occupancies of PPARγ and C/EBPα are critical for whether genes will be induced or repressed by PPARγ agonist.
2013-08-01 | GSE49423 | GEO
Project description:Trophoblasts, as the main part of placenta, undergo cell differentiation including invasion, migration, and fusion. Abnormalities in these processes can lead to a series of gestational diseases whose underlying mechanisms are still unclear. The peroxisome proliferator-activated receptor γ (PPARγ), expressed in the nuclei of extravillous trophoblasts (EVCTs) at the first trimester and villous cytotrophoblasts (VCTs) throughout the pregnancy, is proved to be essential in placentation. We aimed to explore the genome-wide effects of PPARγ on EVCTs and VCTs by the treatment of PPARγ agonist rosiglitazone. EVCTs and CTs were purified from human chorionic villi, followed by primary culture and rosiglitazone treatment. Transcriptomes of EVCTs and VCTs were performed by microarray experiments (Affymetrix and Axon). Owing to the different platforms, threshold for differentially expressed genes (DEGs) detection was performed based on 1.5-fold change and 5% FDR for EVCTs gene expression while 1% FDR was set for VCTs gene expression. Gene ontology (GO) annotation and pathways analysis of DEGs were conducted with ClueGO. PPARγ and DEGs protein interactions predicted by online tool STRING, while PPARγ and DEGs promoters binding sites prediction was conducted by iRegulon. GO and pathway terms were compared between EVCTs and VCTs through ClusterProfiler. Visualization was achieved and modified by Cytoscape. Our microarray data showed that 139 DEGs were detected in rosiglitazone-treated EVCTs (RT-EVCTs) and 197 DEGs in rosiglitazone-treated VCTs (RT-VCTs). Downstream annotation analysis showed the commons and differences between RT-EVCTs and RT-VCTs, including biological process, molecular function, cellular component, KEGG pathway and protein-protein-interaction and transcription factor – target gene binding site prediction. To sum up, our results provide a sight of view to PPARγ-activated trophoblasts performances by giving transcriptomic signatures of the RT-EVCTs and RT-VCTs and make it feasible to acquire more information for further research and find out possible drug-targeted genes or pathways in human placenta.
2020-04-24 | GSE137434 | GEO
Project 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.
2011-03-18 | GSE28031 | GEO
Project 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. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) rosiglitazone-treated 8-month-old apolipoprotein (apoE)-deficient mice with symptoms of heart failure, (ii) untreated 8-month-old apoE-deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.
2011-03-18 | E-GEOD-28031 | biostudies-arrayexpress
Project description:Besides improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best characterized target PPARg has been proposed as a therapeutic option for cancer treatment. In the present study, we reveal a new mechanism by which the thiazolidinedione rosiglitazone contributes to tumorigenesis, which limits its therapeutic potential in cancer. We provide evidence that rosiglitazone activates a tumorigenic paracrine communication program in a subset of human melanoma cells, that involves the secretion of cytokines, chemokines and angiogenic factors. This complex blend of paracrine signals activates non-malignant fibroblasts, endothelial cells and macrophages in a tumor-friendly way. In agreement with these data, we show that rosiglitazone promotes human melanoma development in xenografts, through enhanced angiogenesis and inflammation. Together, these findings establish an important tumorigenic action of rosiglitazone in melanoma cells. While studies conducted on cohorts of diabetic patients report overall benefits of TZDs in cancer prevention, we show that exposure of an established tumor to rosiglitazone may be deleterious.
2020-06-01 | GSE115221 | GEO
Project description:The cellular mechanisms by which PPARγ improves metabolism in mature human adipocytes and potential depot differences in its actions are poorly understood. To assess the global effects of PPARγ activation on human omental gene expression, we conducted microarray analysis of control vs. rosiglitazone-treated omental tissues from human subjects.
2019-04-30 | GSE122721 | GEO
Project description:White adipose tissue regulates metabolism; the importance of this control is highlighted by the ongoing pandemic of obesity and associated complications such as diabetes, atherosclerosis, and cancer. White adipose tissue maintenance is a dynamic process, very little is known about how pharmacologic stimuli affect such plasticity. Combining in vivo lineage marking and BrdU labeling strategies, we found that rosiglitazone, a member of the thiazolidinedione class of glucose-lowering medicines, markedly increases the evolution of adipose progenitors into adipocytes. Notably, chronic rosiglitazone administration disrupts the adipogenic and self-renewal capacities of the stem cell compartment and alters its molecular characteristics. These data unravel unknown aspects of adipose dynamics and provide a basis to manipulate the adipose lineage for therapeutic ends. The goal of this gene expression array was to identify changes in molecular expression in adipose progenitors isolated from mice that underwent two-month rosiglitazone treatment.
2012-01-18 | GSE30116 | GEO