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Status |
Public on Mar 04, 2008 |
Title |
Rosiglitazone effects on kidney gene expression |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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Summary |
Thiazolidinediones increase tissue insulin sensitivity and are protective against worsening of nephropathy and hypertension in diabetes. Mechanisms underlying protection at the renal level likely involve a variety of unknown changes in gene expression. We examined kidney gene expression in obese and lean Zucker rats in response to rosiglitazone (Avandia®), a peroxisome proliferator activated receptor (gamma-subtype) agonist. Lean and obese Zucker rats were treated with either control chow or chow with added rosiglitazone (3 mg/kg•bw) for 12 weeks (n = 3/group). Total kidney mRNA expression was evaluated using the Affymetrix Rat Genome 230 2.0 GeneChip. 903 probe sets were significantly (P < 0.05) altered with at least 1.5-fold changes between groups. In untreated obese rats, 300 probe sets were increased and 244 decreased, relative to lean. Increased genes included the β-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter, and aquaporin 3. Decreased genes included angiotensin converting enzyme, type 1 (ACE1). FatiGO analysis showed that the highest number of altered genes between lean and obese belonged to the categories: ion binding, hydrolase activity, and protein binding. RGZ increased expression of uncoupling protein 1 (UCP1), CD36, and fatty acid binding protein 4 (FAbp4) in both lean and obese rats. In obese rats, 33 genes were normalized by RGZ (no longer different from lean) including ACE1, fatty acid synthase (Fasn), and stearoyl-coenzyme A desaturase 2 (Scd2). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-gamma and tumor necrosis factor alpha (TNF-alpha). Keywords: Thiazolidinediones, PPAR-gamma agonists, renal, type II diabetes, obesity
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Overall design |
Twelve male Zucker rats (6 Lean and 6 Obese) were used in the study. Three rats from each body type were fed either with control diet (ground chow diet) or control diet with rosiglitazone (3 mg/kg body weight). The rats were weighed weekly and fed diets and recieved water ad libitum for 12 weeks.
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Citation(s) |
18700276 |
Submission date |
Mar 05, 2007 |
Last update date |
Jul 31, 2017 |
Contact name |
swasti Tiwari |
E-mail(s) |
st285@georgetown.edu
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Phone |
202-687-8228
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Organization name |
Georgetown University
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Street address |
4000 reservoir road, NW
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City |
washington DC |
State/province |
DC |
ZIP/Postal code |
20057 |
Country |
USA |
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Platforms (1) |
GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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Samples (12)
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Relations |
BioProject |
PRJNA98235 |
Supplementary file |
Size |
Download |
File type/resource |
GSE7193_RAW.tar |
150.3 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data provided as supplementary file |
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