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Series GSE66920 Query DataSets for GSE66920
Status Public on Sep 01, 2016
Title Ketamine suppresses hypoxia-induced inflammatory responses in the late-gestation ovine fetal kidney cortex
Organism Ovis aries
Experiment type Expression profiling by array
Summary Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischemia as a consequence of the physiological redistribution of combined ventricular output. We have demonstrated that hypoxia in late ovine gestation induces inflammation in the brain that is ameliorated by treatment with ketamine. We hypothesized that the fetal kidney would also respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-Methyl-D-aspartate receptor antagonist) would reduce or block this response. Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 down-regulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the down-regulated metabolic responses. We conclude that our transcriptomics modeling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischemic renal damage.
 
Overall design At the time of surgery, fetuses were randomly assigned to one of the four groups (n=3-4/group): normoxic control, normoxia+ketamine, hypoxic control, and hypoxia+ketamine. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125±3 d; term=145-147d), with or without ketamine (3 mg/kg) administered intravenously to the fetus 10 min prior to hypoxia. Fetuses were euthanized 24 hours after the onset of hypoxia, and the kidney cortex were collected for RNA extraction and gene array studies. Gene expression was analyzed using ovine Agilent 15.5 k array and validated with qPCR. Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (P≤0.05).
 
Contributor(s) Chang EI, Rabaglino MB, Zárate MA, Richards EM, Wood CE
Citation(s) 26497972
Submission date Mar 16, 2015
Last update date Dec 02, 2016
Contact name Eileen I. Chang
E-mail(s) change@ufl.edu
Organization name University of Florida College of Medicine
Department Physiology and Functional Genomics
Street address 1345 Center Drive/Room M552
City Gainesville
State/province Florida
ZIP/Postal code 32610-0274
Country USA
 
Platforms (1)
GPL10778 Agilent-019921 Sheep Gene Expression Microarray (Probe Name version)
Samples (15)
GSM1634338 Normoxia_Vehicle_Rep1
GSM1634339 Normoxia_Vehicle_Rep2
GSM1634340 Normoxia_Vehicle_Rep3
Relations
BioProject PRJNA278370

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66920_RAW.tar 40.7 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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