Unknown,Transcriptomics,Genomics,Proteomics

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Gene Expression of Kidney from HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney) using Rat Gene 1.1 ST Array [RaGene-1_1-st]

ABSTRACT: We recently developed a new model of renal agenesis [i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. The HSRA model consistently exhibits unilateral renal agenesis ranging from 50-75% in each generation and is characterized by low nephron number, early kidney hypertrophy, and an inherent susceptibility to develop significant kidney injury and decline in renal function with age. Whole transcriptome analysis was evaluated at month 1 to identify early changes in genes/networks that may be involved in increased susceptibility of HSRA-S to develop kidney injury in the long-term. An n=4 per group (independent samples) were evaluated for HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney). HSRA-C (two-kidney) samples were set as the control.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Michael Garrett

PROVIDER: E-GEOD-62092 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

Dataset Information

Gene Expression of Kidney from HSRA-S (congenital solitary kidney) and HSRA-C (two-kidney) using Rat Gene 1.1 ST Array [RaGene-1_1-st]

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