Time-Dependent miRNA Profiling Following Ischemia/Reperfusion Injury in Rat Retina
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Nigel Cooper
PROVIDER: E-GEOD-61072 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The purpose of the present study was to investigate time-dependent changes in gene expression, following induction of IR in the rat retina, and to characterize the affected pathways, networks and processes. 6 biological replicates with two treatments (Sham control and Ischemia reperfusion) and 3 time points (0h, 24h and 7day)
2013-01-24 | E-GEOD-43671 | biostudies-arrayexpress
Project description:Glaucoma is not only the second leading cause of blindness worldwide, but patient numbers will also increase significantly in the coming years due to aging societies. Glaucoma is a progressive optic neuropathy with changes at the optic nerve head, gradual retinal ganglion cell (RGC) death, and visual field loss [1]. Unfortunately, glaucoma can remain asymptomatic until it is rather far progressed, hence about 10-50 % of patients are unaware they suffer from this disease. High intraocular pressure (IOP) is the main risk factor; however, normal-tension glaucoma (NTG) occurs in patients with physiological IOP [2]. This form account for about 30 % of glaucoma patients [3]. Furthermore, sustained IOP lowering can slow down, but does not completely stop disease progression in patients. [4, 5]. Additionally, the administration of topical glaucoma medications can lead to side effects, such as ocular irritation, decreasing the compliance of patients. These facts emphasize the importance of discovering new treatment strategies. The exact pathogenesis for glaucoma is still unknown, but several factors are considered to be involved (fig.1). The most prominent factor is an elevated IOP, which can cause blockade of axonal protein transport at the lamina cribrosa, causing an initial axonal damage and RGC death by trophic insufficiency. In addition, ischemic/hypoxic damage [6], astrocyte and glia cell alterations, and excessive stimulation of the glutamatergic system [7] are discussed as possible pathomechanisms. Moreover, an involvement of the immune system is considered [8-10]. In glaucoma patients, up- and downregulations in the systemic and ocular antibody profile were detected [11-13]. Also, antibody deposits were observed in glaucomatous retinae [14]. It is likely that a combination of several pathogenic factors/mechanisms increases the possibility of developing glaucoma. For the investigation of pathomechanisms and novel therapies, it is necessary to have suitable models that allow such screening. To investigate whether antibodies detected in glaucoma patients are part of glaucoma pathogenesis or a result of disease progression, the experimental autoimmune glaucoma (EAG) animal model was established. This animal model is based on the fact that autoantibodies against S100B, a small calcium binding protein expressed in glia cells, were found to be increased in glaucoma patients [15]. In this model, an immunization with S100B led to a significant loss of RGCs after 28 days and a fast degeneration of optic nerves [20]. The IOP in this model was not altered. Therefore, we were able to mimic the effects seen in NTG patients, an IOP-independent glaucomatous degeneration, by immunizing rats with S100B. S100B is a calcium-binding protein. In the central nervous system (CNS), it is mainly expressed by glial cells such as oligodendrocytes, Schwann cells, ependymal cells, retinal Müller cells and astrocytes [16]. S100B regulates and maintains the homeostasis of the important second messenger calcium and is therefore involved in many cell activities, such as signal transduction, cell differentiation, regulation of cell motility, transcription and cell cycle processes [17, 18]. Extracellularly, S100B can act as a signal molecule and bind receptors such as the receptor for advanced glycation end products (RAGE). In high concentrations, S100B can have negative effects and lead to cell death. For example, the binding of RAGE can induce the activation of microglia cells leading to a release of proinflammatory cytokines to an excessive extent [19]. Furthermore, there seems to be a link between S100B and neuronal diseases. In glaucoma patients, high antibody titers against S100B were found [20]. To investigate the effect of S100B in glaucoma more precisely, the immunization with S100B leads to a loss of retinal ganglion cells (RGCs) without an elevation of the IOP after 28 days in the EAG model [21, 22]. The goal of the present study was to detect the retinal biomarkers in EAG animals 7 and 14 days after immunization with S100B. To detect these new markers in disease development, a label free quantitative mass spectrometry-based approach will be used.
2022-02-16 | PXD023995 | Pride
Project description:Sprague-Dawley rat retina post-injury and control samples
2007-10-26 | E-GEOD-1001 | biostudies-arrayexpress
Project description:The etiology of trauma-hemorrhage shock-induced acute lung injury has been difficult to elucidate due, at least in part, to the inability of in vivo studies to separate the non-injurious pulmonary effects of trauma-hemorrhage from the tissue injurious ones. To circumvent this in vivo limitation, we utilized a model of trauma-hemorrhagic shock (T/HS) in which T/HS-lung injury was abrogated by dividing the mesenteric lymph duct. In this way, it was possible to separate the pulmonary injurious response from the non-injurious systemic response to T/HS by comparing the pulmonary molecular response of rats subjected to T/HS which did and did not develop lung injury as well as to non-shocked rats. Utilizing high-density oligonucleotide arrays and treatment group comparisons of whole lung tissue collected at 3 hours after the end of the shock or sham-shock period, 139 of the 8,799 assessed genes were differentially expressed. Experiment Overall Design: Four groups of rats (n=3) were studied in order to identify changes in pulmonary gene expression associated with T/HS, both in the presence and absence of lung injury. These included trauma-sham shock (T/SS) rats which had a laparotomy (trauma) but were not subjected to hemorrhagic shock. These rats had no lung injury and served as controls for rats which were subjected to T/HS (laparotomy plus 90 min of shock) and had lung injury. Differences in gene expression between these two groups would represent both the effects of hemorrhagic shock as well as lung injury. To distinguish the gene response of hemorrhagic shock from the gene response associated with lung injury, gene expression was also compared between T/HS rats (hemorrhage and lung injury) and rats subjected to T/HS plus lymph duct ligation (T/HS-LDL), since the T/HS-LDL rats experienced hemorrhagic shock but had no measurable lung injury. Lastly, to identify hemorrhagic shock- modified genes, the pulmonary gene response of T/HS-LDL (hemorrhage without lung injury) were compared to rats subjected to T/SS plus LDL (no hemorrhage or lung injury). Three hours after the end of the 90 min shock or sham-shock period (i.e. 4.5 hrs after the induction of T/HS), the rats were sacrificed and specimens harvested for genechip analysis and histology.
2008-06-14 | E-GEOD-6332 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene expression to control cell growth and differentiation. MiRNA levels are substantially altered in various types of tumors and have been used as biomarkers in defining malignant status. However, studies on responses of miRNA expression to carcinogen insults in their target tissues are rare. In this study, we analyzed miRNA expression in the livers of rats treated with carcinogenic dose of comfrey (Symphytum officinale), a rat botanical carcinogen. Groups of 6 Big Blue Fisher 344 rats were fed a normal diet or a diet containing 8% comfrey root for 12 weeks. The animals were sacrificed one day after the last treatment and the livers were isolated from the control and treated rats for miRNA expression analysis. The miRNA expressions were determined using miRNA microarrays for human, mouse and rat (LC Sciences). Data were normalized using cyclic method and statistically analyzed using Ttest.
2010-12-01 | E-GEOD-22655 | biostudies-arrayexpress
Project description:MicroRNAs are small non-coding RNAs that regulate a variety of biological processes. In the last version of the miRBase database (Release 17), 720 mouse microRNAs are accompanied by only 408 rat microRNAs. Given the importance of rat as a model organism, we used next generation sequencing and microarray technologies to discover novel microRNAs in rat kidneys. Four male, 6-week-old Big Blue rats were treated with 10.0 mg/kg aristolochic acid(AA) 5 times a week for 12 weeks, four untreated rats as control. The animals were sacrificed 1 day after the last treatment and total RNA were isolated. All eight rat samples were used to deep sequencing analyses (University of Texas Southwestern Medical Center Microarray Core Facility), while 6 samples (3 AA-treated and 3 control) were used to custom vertebrate microRNA microarray analysis (LC Sciences). We used the miRanalyzer standalone version for the prediction of novel microRNAs and microRNA microarray to confirm novel microRNAs.
2011-11-02 | E-GEOD-33360 | biostudies-arrayexpress
Project description:Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARa and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal TH homeostasis, in the livers of adult male rats exposed in feed to 50 mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes. Global gene expression changes were consistent with the involvement of PPARα and CAR/PXR in PFOS-induced effects. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122 and miR-21 were the most decreased, in PFOS-treated relative to control rats. Expression of the miR-23b/27b/24 cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes demonstrated enrichment of transcripts involved in epithelial to mesenchymal transition (EMT), which is a primary process involved in tumor cell motility and cancer metastasis. Liver expression analysis revealed transcripts that may mediate PFOS effects on thyroid hormone (TH) homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signalling; suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, PFOS-induced miRNA perturbations were strongly associated with EMT suggesting an important role for miRNAs in PFOS-induced hepatotoxicity. The work also provides novel insights into the effects of PFOS on TH homeostasis. Total RNAs from liver samples (4 animals from each group) were labelled using the miRNA Complete Labelling and Hybridization kit (Agilent Technologies). Labelled RNA was hybridized on 8 X 15K Agilent rat miRNA microarray slides. Arrays were scanned using an Agilent G2505B scanner (5 μm resolution). Agilent Feature Extraction (version 10.7.3.1) was used to acquire the fluorescence intensity of each probe. The quality of the microarray data was evaluated using Agilent Feature Extraction quality control metrics. Data were normalized in R using cyclic-lowess (Bolstad et al., 2003). Ratio-intensity plots, boxplots and cluster analyses were used to identify potential outliers. One control sample failed the quality control tests and was eliminated for subsequent analyses. Statistically significantly altered miRNAs were identified using the methods described above for gene expression.
2015-08-01 | E-GEOD-69521 | biostudies-arrayexpress
Project description:Kidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. 311 miRNAs were found to be expressed in at least one age and sex. Filtering criteria of ?1.5 fold change and ANOVA (FDR <5%) revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2 week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified. Pathway analysis was used to investigate the possible roles of these target genes in age- and sex-specific differences. Untreated male and female F344 rats from 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age (n=5) were sacrificed by CO2 asphyxiation, whole kidneys collected and homogenized, total RNA, including small RNA fraction, was used for miRNA expression arrays (Agilent).
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Project description:Pulmonary hypertension (PH), a rare disorder is a complication of a number of cardiopulmonary, unrelated systemic diseases, drug toxicity and genetic mutations. Major advances have been made in the field, but the pathogenesis of PH is not yet understood. Several experimental models such as monocrotaline (MCT) and hypoxia have been used to understand the mechanism underlying the pathogenesis of PH. We have recently shown that that the addition of hypoxia to MCT injected rats accelerates the disease process leading to neointima formation. We have profiled the lungs of adult male Sprague-Dawley rats kept for 4 weeks in normal atmospheric conditions or in hypobaric hypoxia (380 mmHg) w/o subcutaneous injection with 40 mg/kg MCT or just saline. While MCT and hypoxia altered expression of few genes when applied separately, together they induced a substantial alteration of the transcriptome. The most profoundly altered pathways by the combined effect of hypoxia and MCT were: endocytosis, apoptosis, HIF-1 signaling pathway and vascular smooth muscle contraction. Two-condition (C = normal atmospheric conditions (control) vs H = hypobaric hypoxia) + two treatment (M = with MCT, O = without MCT) experiment. Four biological replicas of each combination: CO, HO, CM, HM. Differently labeled biological replicates were cohybridized with each array. Results of similarly labeled different conditions were compared then averaged for the two fluorescent labels. For instance: CO1 & CO3 were compared with CM1 & CM3, CO2 & CO4 were compared with CM2 & + CM4, and the results of the comparisons averaged. This design uses 100% of the resources, has a better normlaiztion and allows all possible comparisons among the conditions.
2015-09-04 | E-GEOD-72707 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-01 | E-GEOD-69522 | biostudies-arrayexpress