Gene expression regulation by angiotensin II in late gestation fetal sheep
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ABSTRACT:
ORGANISM(S): Ovis aries
SUBMITTER: Timothy Bahr
PROVIDER: E-GEOD-45463 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:In order to characterize gene expression networks linked to AT1 angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1A receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. At baseline, 405 genes were differentially expressed (>1.5X) between WT and KO kidneys. Of these, more than 80% were up-regulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ~805 genes was altered (18% up-regulated, 82% repressed). Genes in metabolism and ion transport pathways were up-regulated while there was attenuated expression of protective genes against oxidative stress including glutathione synthetase and mitochondrial SOD2. Angiotensin II infusion has little effect on blood pressure in KOs. Nonetheless, expression of more than 250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were up-regulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation. To define gene expression patterns in kidney triggered by of activation AT1 receptors, we used genome-wide transcriptional analysis of RNA from kidneys of wild-type and AT1A receptor-deficient mice at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. All of the experiments were conducted with male mice 2.5 months old and included 3 mice per experimental group. Synthesis of cRNA, hybridization and scanning of chips were conducted by Duke University microarray core facility (Duke University, Durham, NC).
2010-09-30 | E-GEOD-18430 | biostudies-arrayexpress
Project description:Hypertension induced with chronic or acute angiotensin treatment in mouse
2005-01-01 | E-TIGR-11 | biostudies-arrayexpress
Project description:Amniotic fluid volume (AFV) is determined primarily by the rate of intramembranous (IM) transport of AF cross the amnion. Intramembranous transport is characterized as vesicular endocytotic and transcytotic processes regulated by fetal urine-derived stimulators and AF inhibitors. Our objectives were to utilize a large-scale multiomics approach to decipher the vesicular transport pathways in the amnion and to identify potential transport regulators in AF and fetal urine. We utilized fetal sheep to experimentally induce alterations in IM transport rate and analyze the expression profiles of transcripts and proteins in amnion, AF and fetal urine. Four experimental groups were studied: control (C), urine drainage with reduced IM transport rate and AFV (UD), urine drainage and fluid replacement with decreased IM transport rate but increased AFV (UDR), and intra-amniotic fluid infusion with increased IM transport rate and AFV (IA). Amnion and fluid samples were subjected to transcriptomics (RNA-Seq) and isobaric labeling proteomics studies followed by bioinformatics analyses using Ingenuity Pathway Analysis software. The analyses revealed 9 functional transport pathways and a panel of differentially expressed transcripts and proteins that are known mediators of vesicular transport and cellular trafficking. During UD, expression of transport and trafficking mediators were reduced as compared to controls. With UDR, expression of energy metabolism activators increased while trafficking mediators decreased. During IA, expression of vesicular uptake molecules increased while trafficking mediators decreased. Co-expression of the motor protein, cytoplasmic dynein light chain-1, in both AF and fetal urine suggest that this molecule may function as a urine-derived stimulator of IM transport.
2021-07-21 | PXD013135 | Pride
Project description:Hypertension induced with chronic or acute angiotensin treatment in mouse. Related experiment E-TIGR-11
2005-01-01 | E-TIGR-12 | biostudies-arrayexpress
Project description:Gliomas are aggressive primary brain tumors, presenting surgery limitations due to their highly infiltrative potential. The expression of Angiotensin II (Ang II) receptors in human astrocytomas was previously associated with a poor prognosis. Accordingly, this study was undertaken to reveal the molecular mechanisms underlying Ang II actions in gliomas through the transcriptomic analysis of glioma cells exposed to Ang II. C6 glioma cells were treated with Ang II and specific antagonists of AT1 and AT2. Total RNA was isolated at three and six hours intervals and submitted to oligonucleotide microarray protocol. The differentially expressed genes were obtained by paired t-tests with p<0.05 and interpreted using Venn diagrams, functional enrichment and protein interaction network analyses. Validation of microarray results was carried out through qPCR experiments of selected genes. We found a high number of significant genes with low fold changes in gene expression at the time intervals studied. These genes were regulated in a time dependent-manner, with most gene expression changes being exclusive to one of the time intervals evaluated. Our results indicated that blocking AT1 or AT2 changed the expression of genes involved in regulation of transcription, cell cycle, cell proliferation, differentiation, apoptosis, cell adhesion, cell migration, regulation of actin cytoskeleton, protein transport and protein ubiquitination. Additionally, the signaling pathways over-represented by the significant genes were ErbB, mTOR, MAPK, neurotrophin, insulin and Wnt. Finally, interactome analyses revealed hub genes associated with cell proliferation, survival, migration, transport, structural support, neurotrophin pathway, MAPK signaling and Wnt signaling. Taken together, our findings implicate Ang II-transcriptional regulation in glioma progression by means of the modulation of genes participating in protumoral functions. This transcriptome pattern is observed upon Ang II activation of either AT1 or AT2 receptors, thereby highlighting the relevance of both receptor subtypes in glioma progression. Interactome analyses disclosed hub genes regulated by Ang II which may present higher control over their networks. These genes participate in biological functions that could enhance the degree of malignancy in gliomas and thus should be further explored. C6 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum, 100 Units/ml penicillin and 100 M-BM-5g/ml streptomycin. Cells were seeded in cell culture dishes and incubated at 37M-BM-0C/ 5% CO2 until becoming confluent. Then, these cells were pre-treated (30 minutes) with either AT1 receptor antagonist (Losartan: 10-5M) or AT2 receptor antagonist (PD123319: 10-5M) followed by Ang II treatment (10-7 M) according to the treatment scheme: Group 1 M-bM-^@M-^S control; Group 2 M-bM-^@M-^S cells only treated with Ang II; Group 3 M-bM-^@M-^S cells pre-treated (30 minutes) with Losartan and then treated with Ang II; Group 4 M-bM-^@M-^S cells pre-treated (30 minutes) with PD123319 and then treated with Ang II. To identify which genes were significantly differentially expressed, paired t-tests (p<0.05) were performed in the following comparisons: Ang II x Control (3h); Ang II x Control (6h); Ang II +Los x Ang II (3h); Ang II +Los x Ang II (6h); Ang II +PD123319 x Ang II (3h); Ang II +PD123319 x Ang II (6h).
2014-12-20 | E-GEOD-47529 | biostudies-arrayexpress
Project description:Angiotensin II (Ang II) mediated signaling plays a key role in the development of hypertension associated target organ damages. However, the gene expression changes regulated by Ang II in the early stage of acute cerebral, cardiac, renal, vascular injury remain unclear. we investigated Ang IIâ??mediated gene expression alteration associated with the development of early cerebral, cardiac, renal, vascular injury by microarray assay in a mouse model. All mice were euthanized by an overdose of pentobarbital on days 1, 3 and 7 of Angiotensin II treatment. Total RNA was isolated with TRIzol (Invitrogen) from brains, hearts, kidneys and vessels (n=1-3 per group) at each time point according to manufacturerâ??s instructions. Gene expression profiling was performed using Affymetrix GeneChip mouse Genome 430 2.0 array according to the manufacturerâ??s instructions (Affymetrix, Inc., Santa Clara, CA). On the GeneChip Mouse Genome 430 2.0 Array, over 45,000 probe sets analyze the expression level of over 39,000 transcripts and variants from over 34,000 well characterized mouse genes.
2014-07-16 | E-GEOD-59437 | biostudies-arrayexpress
Project description:Rats (Wag/Rij, females) were chronically treated with Losartan (20mg/d), an angiotensin II-receptor blocker during 9 months. Gene expression profiling was performed on aortic media to understand the long-term effect of this molecule on the cardiovascular system. Two-conditions experiment, Ctrl vs Losartan-treated animals. Biological replicates: 5 control replicates, 5 Losrtan-treated animals. All the RNA samples were pooled to provide a reference RNA for a two-color experiment.
2010-09-23 | E-GEOD-18298 | biostudies-arrayexpress
Project description:Background: The aim of this study is to improve our understanding of the mechanisms underlying the sparing of masticatory muscles in ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factors triggering AQM, such as muscle unloading, endotoxin-induced sepsis, and systemic exposure to CS and NMBA. Results: An increased expression was notably observed in atrogin-1, cathepsins, FoxO1a, runx1 and heat-shock proteins genes. A decreased expression in some sarcomeric proteins and myostatin genes was also noticed. Hence, modifications in heat-shock proteins and myostatin genes are in sharp contrast to alterations in the limb muscles and it is postulated that elevated heat-shock proteins and decreased myostatin genes play a protective role in the masticatory muscle in ICU patients with AQM. Conclusions: We have observed a general down-regulation of muscle proteins and myostatin. Genes involved in the UPS system, cathepsins, RUNX1, TBX1, TIMP2 and transcripts of heat-shock proteins were up-regulated. However, we have neither observed a decrease in fiber CSA or force generation, suggesting that the expected atrophic changes have been countered by a protective mechanism and myostatin downregulation. Five female domestic piglets were treated with non-depolarizing neuromuscular blocking agents (NMBA), corticosteroids(CS) and sepsis. Five female piglets were untreated.
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Project description:The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage. This is a comparison between the renin inhibitor aliskiren with the At1 antagonist losartan in mice with chronic kidney disease due to renal ablation. Renal tissue from ablated mice was used after 6-week treatment with either 500 mg/l losartan or 50 mg/kg aliskiren per day (n = 5)
2012-11-05 | E-GEOD-34552 | biostudies-arrayexpress