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SRP042085
Mus musculus
16 Downloadable Samples
Illumina Genome Analyzer, Illumina HiSeq 2000
Description
Estrogen has vascular protective effects in premenopausal women and in women under 60 receiving hormone replacement therapy. However, estrogen also increases risks of breast and uterine cancers and of venous thromboses linked to upregulation of coagulation factors in the liver. In mouse models, the vasoprotective effects of estrogen are mediated by the estrogen receptor alpha (ERa) transcription factor. Here, through next generation sequencing approaches, we show that almost all of the genes regulated by 17-b-estradiol (E2) differ between mouse aorta and mouse liver, and that this is associated with a distinct genomewide distribution of ERa on chromatin. Bioinformatic analysis of E2-regulated promoters and ERa binding site sequences identify several transcription factors that may determine the tissue specificity of ERa binding and E2-regulated genes, including the enrichment of NFkB, AML1 and AP-1 sites in the promoters of E2 downregulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggests ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. Our results also highlight the likely importance of rapid signaling of membrane-associated ERa to cellular kinases (altering the activities of transcription factors other than ER itself) in determining tissue specific transcriptional responses to estrogen. Overall design: The aortas or liver fragments of wild-type C57/BL6 mice were incubated ex vivo with 10nM E2 or ethanol vehicle for 4 hours before harvesting for RNA collection. Each condition was performed with two biological replicates, and each replicate contained aortas or liver fragments from 4 mice.
Publication Title
Research resource: Aorta- and liver-specific ERα-binding patterns and gene regulation by estrogen.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
MicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We now demonstrate that endogenous and over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). We report that the seed region of moR-21 as well as the seed match region in the target gene 3'UTR are indispensable for moR-21-mediated gene down-regulation. We further demonstrated that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. Taken together, these findings provide the first evidence that microRNA offset RNA regulates gene expression and is biologically active.
Publication Title
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Background: Clinical trial and epidemiological data support that the cardiovascular effects of estrogen are complex, including a mixture of both potentially beneficial and harmful effects. In animal models, estrogen protects females from vascular injury and inhibits atherosclerosis. These effects are mediated by estrogen receptors (ERs), which when bound to estrogen can bind to DNA to directly regulate transcription. ERs can also activate several cellular kinases by inducing a rapid non-nuclear signaling cascade. However, the biologic significance of this rapid signaling pathway has been unclear.
Publication Title
Rapid estrogen receptor signaling is essential for the protective effects of estrogen against vascular injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Infliximab, an anti-TNF-alpha monoclonal antibody, is an effective treatment for ulcerative colitis (UC) with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-TNF-alpha is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in UC.
Publication Title
Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Infliximab, an anti-TNFa monoclonal antibody, is an effective treatment for ulcerative colitis (UC) inducing over 60% of patients to respond to treatment. Consequently, about 40% of patients do not respond. This study analyzed mucosal gene expression from patients enrolled in ACT1 to provide a predictive response signature for infliximab treatment.
Publication Title
Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 9 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
Ischemic heart failure after acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a trans-valvular axial-flow pump in the LV and delaying myocardial reperfusion, known as Primary Unloading, limits infarct size by reducing LV wall stress and increasing expression of the cardioprotective cytokine, stromal derived factor 1 alpha (SDF1a). The mechanisms underlying the cardioprotective benefit and sustained effect of Primary Unloading remain poorly understood. We now tested the importance of delayed reperfusion, the functional significance of SDF1a, and the late-term impact on myocardial function and scar size associated with Primary Unloading.
Publication Title
Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 40 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
Previous data suggest that 2-cysteine peroxiredoxin, cyclophilin 20-3 and the cysteine synthase complex work as a dynamically interacting module (here named COPS-module) and are involved in stress response. In this study we performed global transcriptome analyses to investigate the responses to short-term high light in wildtype and mutants deficient in each protein of COPS-module.
Publication Title
The redox-sensitive module of cyclophilin 20-3, 2-cysteine peroxiredoxin and cysteine synthase integrates sulfur metabolism and oxylipin signaling in the high light acclimation response.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Fetal mice (16 days gestation) were administered feline immunodeficiency virus (FIV)-based lentiviral viral particles containing the gene encoding GFP. Six liver tumors developed in three mice between the ages of 273 and 484 days, each mouse developed 2 tumors. These tumors and non-tumorous liver tissue from the same animals and animals that did not develop tumors and untransduced controls were harvested and microarrays were performed on total RNA extracted from these samples. We were interested in investigating the link between lentiviral integration and gene expression.
Publication Title
Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1 and AMPK2. The muscle transcriptome of the non-responders is further characterized by an activation of TGF and TGF target genes, which is associated with increases in inflammatory and macrophage markers. TGF1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF1 signaling down-regulates the abundance of PGC1, AMPK2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGF activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.
Publication Title
TGF-β Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.
Sample Metadata Fields
Specimen part
View Samples