Fibrinogen is upregulated following kidney damage and protects it against ischemia-reperfusion injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Vishal Vaidya
PROVIDER: E-GEOD-27274 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:characterization of fibrinogen expression in the kidney, excretion in the urine following kidney damage and evaluating the therapeutic potential of fibrinogen in acute kidney injury.
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Project description:Ischemic preconditioning is effective in limiting subsequent ischemic acute kidney injury in experimental models. microRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. An evaluation was performed of the time- and dose-dependent effects of ischemic preconditioning in a rat model of functional (bilateral) ischemia-reperfusion injury. A short, repetitive sequence of ischemic preconditioning resulted in optimal protection from subsequent ischemia-reperfusion injury. A detailed characterization of microRNA expression in ischemic preconditioning/ischemia-reperfusion injury was performed by small RNA-Seq.
2021-12-31 | E-MTAB-9896 | biostudies-arrayexpress
Project description:Ischemic preconditioning is effective in limiting subsequent ischemic acute kidney injury in experimental models. microRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. An evaluation was performed of the time- and dose-dependent effects of ischemic preconditioning in a rat model of functional (bilateral) ischemia-reperfusion injury. A short, repetitive sequence of ischemic preconditioning resulted in optimal protection from subsequent ischemia-reperfusion injury. A detailed characterization of microRNA expression in ischemic preconditioning/ischemia-reperfusion injury was performed by Exiqon miRCURY microRNA array.
2021-12-31 | E-MTAB-9900 | biostudies-arrayexpress
Project description:Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.7±1.8) and Dex (2.3±1.2) was reduced (P<0.05) compared to Vehicle (3.8±0.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to uninjured/untreated control (0.14±0.26) group. At 24h post-IR urine Lipocalin-2 (µg/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67±o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.7±1.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6± 1.5) compared to Vehicle (Grade 2.9±1.1) group. Inflammatory cytokines IL1β and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury. We had three experimental groups. Group A, VPA treatment; Group B, Dexamethasone treatment; and Group C, No treatment (vehicle saline control). Treatments were administered prior to the induction of left renal ischemia. Animals underwent 45 minutes of left renal ischemia, followed by reperfusion, and right nephrectomy as described above. Following reperfusion, animals were sacrificed at 3, 24 or 120 hours (n=8/group). In the 3 hour group, rats were maintained under anesthesia after surgery until sacrifice. In the 24 and 120 hour groups, the rats were recovered and returned to the cages for normal housing. Analgesic buprenorphine (0.05mg/kg) was administered every 12 h for three days post-operatively. After animal sacrifice, urine, blood, and kidney were collected for kidney functional biomarker assays, histology and / or molecular analyses. Urine was obtained via cystocentesis and blood was obtained via the left renal vein. Tissue and urine samples collected from normal (naïve) animals (n=5) were used for baseline measurements. A subset of 46 animals (n = 4-5 per group) were selected for microarray analysis.
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Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemia reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and preserved using hypothermic machine perfusion with cold University of Wisconsin solution with/without the addition of heparinoids low molecular weight heparin and pentosan polysulfate (PPS) followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer to simulate early ischaemia reperfusion injury (IRI). The donor rats consisted of a control group cold perfusion group compared to warm perfusion and groups treated with either low molecular weight heparin or PPS to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment Donor kidneys were harvested and preserved by hypothermic machine perfusion with University of Wisconsin (UW) Solution for 3 hours followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer for 30 minutes to simulate transplantation and whole blood ischaemia reperfusion injury. The model was then used to test the anti-inflammatory properties of the glycosaminoglycan heparin and PPS when used as supplements into perfusate solutions. Half of the donor kidney was used to extract RNA using the Tri reagent and stored in RNA Later. The qualitative best three RNAs from each group were quantified by fluorimetry and mixed in an equimolar manner and used for microarray analysis.
2012-03-22 | E-GEOD-36671 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE10652: Divergent genome expression profiles during hepatic ischemia in young and adult mice GSE10654: Age-dependent gene expression profiles after hepatic ischemia/reperfusion in mice Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10657 | biostudies-arrayexpress
Project description:Acute renal failure (ARF) has high morbidity and mortality. In animal ARF models, effective treatments must be administered before or shortly after the insult, limiting their clinical potential. We used microarrays to identify early biomarkers that distinguish ischemic from nephrotoxic ARF, or that detect both injury types. We compared rat kidney transcriptomes 2 and 8 hours after ischemia/reperfusion and after mercuric chloride. Quality control and statistical analyses were necessary to normalize inter-experimental groups, eliminate outliers, and exclude unaltered genes. Principal component analysis revealed distinct ischemic and nephrotoxic trajectories, and clear array groupings. Therefore, we used supervised analysis, t-tests and fold changes, to compile gene lists for each group, exclusive or non-exclusive, alone or in combination. We used two lots of microarrays (Lot 1, n = 24, Lot 2, n = 12), for a total of 36 microarrays. Five of them were duplicates, where two aliquots of RNA from the same rat were processed independently and hybridized to separate microarrays. Normal rats were used in both lots (n = 3 for each lot) for normalization.
2010-07-01 | E-GEOD-3219 | biostudies-arrayexpress
Project description:Experimental Design: 1. The goal of the experiment: Age-Dependent Gene Expression Profiles After Hepatic Ischemia/Reperfusion: Implications for the AP-1 and Ubiquitin-Proteosome Pathways 2. Brief description of the experiment: Hepatic ischemia/reperfusion (I/R) injury is a complication of liver surgery, transplantation and shock. Our previous studies have suggested there is an age-dependent response to I/R. In the present study, we examined global gene expression after liver I/R in young (4-5 weeks) and adult (12-14 months) mice using Affymetrix microarray. Gene expression was filtered based on a change in expression of 1.5-fold relative to respective controls and then analyzed by ANOVA. Seventy-two genes in young mice and 56 genes in adult mice had significantly increased expression. Of these, only 18 were up-regulated in both age groups. In young mice, 289 genes were down-regulated whereas in adult mice, 874 genes were decreased. Of these genes, 175 genes were decreased in both groups. Pathway and network analyses of up- and down-regulated gene lists revealed a number of notable differences between young and adult mice. Of these, we found that genes related to the activating protein-1 (AP-1) pathway were upregulated preferentially in young mice. This corresponded with an increase in AP-1 activation in young versus adult mice. Finally, we found that genes related to the ubiquitin-proteasome pathway were selectively down-regulated in adult mice. This was accompanied by reduced degradation of the inhibitory protein, I?B?, in adult mice. The data demonstrate specific, pathway- and network-related differences in gene expression profiles between young and adult mice in the response to I/R. More specifically, we have identified two pathways that may contribute to the superior response to I/R in young mice which represent potential therapeutic targets. Keywords: treated vs non treated 2 age groups of 6 young and 6 adult mice that underwent either 90 minutes of partial ischemia followed by 1 hour of reperfusion (n=3) or sham operation (n=3) We used microarray to uncover the genomic response after ischemia reperfusion in 2 different age groups
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