Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo mouse model.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23163 | GEO | 2011/01/10
SECONDARY ACCESSION(S): PRJNA131551
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE23160: Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo wild-type mouse model. GSE23162: Global transcriptomic profiling of ischemic/reperfusion injury in an in vivo Gpx1 -/- transgenic mouse model. Refer to individual Series
2011-01-10 | E-GEOD-23163 | biostudies-arrayexpress
Project description:Ischemic stroke triggers severe focal hypoperfusion accompanied with deprivation of oxygen and glucose to the cerebral tissue, together with loss of ATP, depolorization of neurons, elevated extracellular potassium concentration, and subsequently leads to excitotoxicity as well as increased oxidative stress promoting microvascular injury, blood-brain-barrier deregulation, post-ischemic inflammation and eventually the consequential neurological deficit. Although reperfusion of ischemic brain tissue is critical for restoring normal function, it can paradoxically result in secondary damage, called ischemia/reperfusion (I/R) injury. Microarray analysis was performed on the right striatum and cortex (corresponded to infarct area) of post-I/R injured brain tissues of wild-type (WT-MCAO) using Illumina mouse Ref8 V2 genechips. Suture-induced middle cerebral artery occlusion was induced for 2h followed by reperfusion, with tissue extraction taking place 2h, 8h and 24h post-reperfusion (n=4 respectively). Sham controls were included in this study too (n=4 respectively).
2011-01-10 | E-GEOD-23160 | biostudies-arrayexpress
Project description:Glutathione peroxidase (Gpx) is a selenium-containing enzyme that catalyses the reduction of a variety of biological peroxides at the expense of reduced glutathione (GSH). Gpx1 is the most abundant isoform and its role has been implicated in neurodegenerative disorders such as ParkinsonM-bM-^@M-^Ys disease (PD), dementia with Lewy bodies tissue (DLB) (Power and Blumbergs, 2009) and traumatic brain injury (Tsuru-Aoyagi et al., 2009). Due to its high abundance, mutation of the Gpx1 allele would lower overall Gpx activity in the brain significantly. Gpx1 knockout (Gpx1-/-) mice do not show overt phenotypic differences, but all indications suggest that these mice are in a chronic M-bM-^@M-^\pro-oxidantM-bM-^@M-^] state (Cheng et al. 1999; de Haan et al. 2004). Indeed, a recent study from our laboratory illustrated that the absence of Gpx1 exacerbated stroke injury via increased ROS production and vascular permeability (Wong et al. 2008). Furthermore, Gpx1-/- mice demonstrated an increase in caspase-3 activation and greater infarct volume (Crack et al. 2001) Microarray analysis was performed on the right striatum and cortex(corresponded to infarct area) of post-I/R injured brain tissues of Gpx1 -/- brains using Illumina mouse Ref8 V2 genechips. Suture-induced middle cerebral artery occlusion was induced for 2h followed by reperfusion, with tissue extraction taking place 2h, 8h and 24h post-reperfusion (n=4 respectively). Sham controls were included in this study too (n=4 respectively).
2011-01-10 | E-GEOD-23162 | biostudies-arrayexpress
Project description:Glutathione peroxidase (Gpx) is a selenium-containing enzyme that catalyses the reduction of a variety of biological peroxides at the expense of reduced glutathione (GSH). Gpx1 is the most abundant isoform and its role has been implicated in neurodegenerative disorders such as Parkinson’s disease (PD), dementia with Lewy bodies tissue (DLB) (Power and Blumbergs, 2009) and traumatic brain injury (Tsuru-Aoyagi et al., 2009). Due to its high abundance, mutation of the Gpx1 allele would lower overall Gpx activity in the brain significantly. Gpx1 knockout (Gpx1-/-) mice do not show overt phenotypic differences, but all indications suggest that these mice are in a chronic “pro-oxidant” state (Cheng et al. 1999; de Haan et al. 2004). Indeed, a recent study from our laboratory illustrated that the absence of Gpx1 exacerbated stroke injury via increased ROS production and vascular permeability (Wong et al. 2008). Furthermore, Gpx1-/- mice demonstrated an increase in caspase-3 activation and greater infarct volume (Crack et al. 2001)
2011-01-10 | GSE23162 | GEO
Project description:Ischemic stroke triggers severe focal hypoperfusion accompanied with deprivation of oxygen and glucose to the cerebral tissue, together with loss of ATP, depolorization of neurons, elevated extracellular potassium concentration, and subsequently leads to excitotoxicity as well as increased oxidative stress promoting microvascular injury, blood-brain-barrier deregulation, post-ischemic inflammation and eventually the consequential neurological deficit. Although reperfusion of ischemic brain tissue is critical for restoring normal function, it can paradoxically result in secondary damage, called ischemia/reperfusion (I/R) injury.
2011-01-10 | GSE23160 | GEO
Project description:Ischemic postconditioning (IPO) attenuates hepatic ischemia/reperfusion (I/R) injury. However, little is known about the underlying biological pathophysiology, which could be, at least in part, informed by exploring the transcriptomic changes using next-generation RNA sequencing (RNA-Seq). In this study, 18 mice (C57BL/6) were involved and randomly assigned to three groups: normal (n=6), I/R (n=6, subjected to 70% hepatic I/R), and IR+IPO (n=6, applying IPO to mice with I/R injury). We randomly selected 3 mice per group and extracted their liver tissues for next-generation RNA-Seq. We performed a bioinformatics analysis for two comparisons: normal vs. I/R and I/R vs. IR+IPO. From the analysis, 2416 differentially expressed genes (DEGs) were identified (p < 0.05 and fold change ? 1.5). Gene ontology (GO) analysis revealed that these genes were mainly related to cellular metabolic processes, nucleic acids and protein binding processes. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the DEGs were the mitogen-activated protein kinase (MAPK), IL-17 signalling pathway, regulating pluripotency of stem cells, and insulin resistance pathway. Validation of 12 selected DEGs by qRT-PCR showed that Cyr61, Atf3, Nr4a1, Gdf15, Osgin1, Egr1, Epha2, Dusp1, Dusp6, Gadd45a and Gadd45b were significantly amplified. Finally, a protein-protein interaction (PPI) network constructed to determine interactions of these 11 DEGs. In summary, by exploring gene expression profiling in regard to hepatic I/R and IPO using next-generation RNA-Seq, we suggested a few progression-related genes and pathways, providing some clues for future experimental research.
| S-EPMC6367534 | biostudies-literature
Project description:Hepatic ischemia-reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia-reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia-reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondrial function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia-reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic IR injury.
| S-EPMC4747576 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-31 | E-GEOD-23333 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-12-31 | GSE23333 | GEO
Project description:Acute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray. A construct containing the CAGGS promoter driving eGFP-L10a, with a loxP-site flanked triple SV40 polyA cassette between promoter and eGFP-L10a cassette was targeted into the ubiquitously active Rosa26 locus. The upstream polyA cassette is designed to block activity of the downstream eGFP-L10a cassette. CRE-dependent removal of this transcriptional block activates eGFP::L10a production within the CRE-producing cell, and all of its descendants. Mice carrying the conditional eGFP-L10a allele, referred to as L10a, were maintained in a homozygous state. L10a mice were crossed to four CRE strains to activate eGFP::L10a expression in four predominantly non-overlapping cellular compartments in the kidney. A Six2-Tet-GFP::CRE allele is active exclusively within nephron progenitors; consequently, historical labeling results in eGFP::L10a expression throughout the main body of the nephron. A Foxd1-GFP::CRE allele is active in the progenitors of many of the interstitial cell lineages including those generating mesangial and non-glomerular pericytes. In addition, Foxd1 is normally expressed in podocytes. Cdh5-CRE is reported to be active throughout the vascular endothelium, and finally, Lyz2-CRE specifically labels cells of the myeloid lineage, notably macrophages, monocytes and dendritic cells. Mice carrying any CRE allele and the L10a allele are designated generically CRE-L10a. six2-L10a, foxd1-L10a, cdh5-L10a and lyz2-L10a denote specifically mice that are compound heterozygotes for the indicated CRE driver and L10a. CRE-L10a, L10a heterozygous littermates without CRE allele, C57BL/6 wild type mice were subjected to renal bilateral warm ischemia 28 minutes followed by 24-hour reperfusion when the kidney TRAP RNA and total RNA were isolated and subjected to Affymetrix microarray. Biological triplicates for each CRE-L10a line underwent no Surgery; sham Surgery and IRI treatment.
2014-03-06 | E-GEOD-52004 | biostudies-arrayexpress