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SRP071570
Mus musculus
30 Downloadable Samples
Illumina HiSeq 2500
Description
Photoreceptor degeneration is the central event leading to visual impairment or blindness in most retinal diseases. However, the discovery of safe and effective therapeutic strategies conferring photoreceptor protection remains challenging. A systems pharmacology approach, synergistically targeting distinct cellular pathways could provide an effective strategy for evaluating, preventing or treating retinal dystrophies. Here this concept was investigated using a mouse model of light-induced retinal degeneration. We show that a combination of FDA-approved drugs acting on different G protein-coupled receptors in a synergistic manner could protect retinas against light-induced degeneration when each drug in the combination treatment was administered at a sub-therapeutic dose. Furthermore, transcriptome analyses demonstrated that such combined treatments also preserved patterns of retinal gene expression more characteristic of the normal retina than did single therapies at higher doses. The current study thus supports a new systems pharmacology approach that may extend to other complex neurodegenerative disorders in addition to retinal diseases. Overall design: Male and female Abca4-/-Rdh8-/- at the age of 4- to 6-weeks were used for the current study. All mice were housed and maintained in a 12 h light (=10 lux)/12 h dark cyclic environment in the Animal Resource Center at the School of Medicine, Case Western Reserve University (CWRU). Bright light-induced retinal damage was generated by exposing Abca4-/-Rdh8-/- mice to white light delivered at 10,000 lux (150 W spiral lamp, Commercial Electric) for 30 min. All indicated treatments were administered by intraperitoneal injection 30 min prior to bright light exposure and retinas collected one day later. Single compounds and their tested doses were: 2-Bromo-a-ergocryptine methanesulfonate salt (BRM), metoprolol tartrate (MTP), tamsulosin (TAM), and doxazosin (DOX). Combined treatments were: BRM, MTP and TAM (BMT), or MTP, DOX, and BRM (MDB). Processed data files (linked as series supplementary files): DE_combined.txt; Significant differential expression results from the combined pretreatment experiment. DE_mono.txt; Significant differential expression results from the mono pretreatment experiment. eXpress_counts_combined.txt; Quantitation output from eXpress of effective counts from the combined pretreatment experiment. eXpress_counts_mono.txt; Quantitation output from eXpress of effective counts from the mono pretreatment experiment. eXpress_fpkm_combined.txt; Quantitation output from eXpress of fpkm values from the combined pretreatment experiment. eXpress_fpkm_mono.txt; Quantitation output from eXpress of fpkm values from the mono pretreatment experiment. normalized_fpkm_combined.txt; TMM normalized fpkm values from the combined pretreatment experiment. normalized_fpkm_mono.txt; TMM normalized fpkm values from the mono pretreatment experiment.
Publication Title
Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration.
Sample Metadata Fields
Specimen part, Subject, Compound
View Samples- Mus musculus
- 5 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Appropriate regulation of hematopoietic stem cell (HSC) self-renewal is critical for the maintenance of life long hematopoiesis. However, long-term repeated cell divisions induce the accumulation of DNA damage, especially at telomere, significantly compromises HSC function. Therefore, shelterin elements Pot1a is required to prevent DNA damage response at telomeres in order to maintain their function.
Publication Title
The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We previously showed that a diet containing phloridzin suppressed the blood glucose levels in streptozotocin-induced diabetic mice most likely by inhibiting glucose absorption from the small intestine. In this study, we showed that 0.5% and 1% phloridzin diets significantly reduce the blood glucose levels in healthy normal BALB/c mice after 7 days of feeding.
Publication Title
Phloridzin reduces blood glucose levels and alters hepatic gene expression in normal BALB/c mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury.
Publication Title
Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We showed that diets containing 0.1% or 0.5% quercetin lowered the STZ-induced increase in blood glucose levels and improved plasma insulin levels. A cluster analysis of the hepatic gene expressions showed that 0.5% quercetin diet suppressed STZ-induced alteration of gene expression. Gene set enrichment analysis (GSEA) and quantitative RT-PCR analysis showed that the quercetin diets had their greatest suppressive effect on the STZ-induced elevation of expression of cyclin dependent kinase inhibitor p21(WAF1/Cip1) (Cdkn1a).
Publication Title
Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Phloridzin is a dihydrochalcone typically contained in apples. A diet containing 0.5 % phloridzin significantly improves hyperglycemia but not hypoinsulinemia and tissue lipid peroxidation in streptozotocin (STZ)-induced diabetic mice after 14 days. The phloridzin diet has no effect on the alteration of hepatic gene expression in STZ-induced diabetic mice.
Publication Title
Dietary phloridzin reduces blood glucose levels and reverses Sglt1 expression in the small intestine in streptozotocin-induced diabetic mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet.
Publication Title
Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Peripheral arterial disease (PAD) is a relatively common manifestation of systemic atherosclerosis that leads to progressive narrowing of the lumen of leg arteries. Circulating monocytes are in contact with the arterial wall and can serve as reporters of vascular pathology in the setting of PAD. We performed gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with PAD and controls without PAD to identify differentially regulated genes. We identified 87 genes differentially expressed in the setting of PAD; 40 genes were upregulated and 47 genes were downregulated. We employed an integrated bioinformatics pipeline coupled with literature curation to characterize the functional coherence of differentially regulated genes. Notably, upregulated genes mediate immune response, inflammation, apoptosis, stress response, phosphorylation, hemostasis, platelet activation and platelet aggregation. Downregulated genes included several genes from the zinc finger family that are involved in transcriptional regulation. These results provide insights into molecular mechanisms relevant to the pathophysiology of PAD.
Publication Title
Gene expression profiling of peripheral blood mononuclear cells in the setting of peripheral arterial disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Pulmonary alveoli are complex architectural units thought to undergo endogenous or pharmacologically induced programs of regeneration and degeneration. To study the molecular mechanism of alveoli loss mice were calorie restricted at different timepoints. Lungs were harvested and processed for RNA extraction.
Publication Title
Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
It has been shown that dexamethasone (Dex) impairs the normal lung septation that occurs in the early postnatal period. Treatment with retinoic acid (ATRA) abrogates the effects of Dex. To understand the molecular basis for the Dex indiced inhibition of the formation of the alveoli and the ability of ATRA to prevent the inhibition of septation, gene expression was analyzed in 4-day old mice treated with diluent (control), Dex-treated and ATRA+Dex-treated.
Publication Title
DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation.
Sample Metadata Fields
No sample metadata fields
View Samples