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Gene expression profiling of potential PPARgamma target genes in mouse aorta. Physiol Genomics 2004 Jun 17;18(1):33-42

Date

04/01/2004

Pubmed ID

15054141

DOI

10.1152/physiolgenomics.00027.2004

Scopus ID

2-s2.0-4243120941 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

Diminished activity of peroxisome proliferator-activated receptor-gamma (PPARgamma) may play a role in the pathogenesis of hypertension and vascular dysfunction. To better understand what genes are regulated by PPARgamma, an experimental data set was generated by microarray analysis, in duplicate, of pooled aortic mRNA isolated from mice treated for 21 days with a PPARgamma agonist (rosiglitazone) or vehicle. Of the 12,488 probe sets present on the array (Affymetrix MG-U74Av2), 181 were differentially expressed between groups according to a statistical metric generated using Affymetrix software. A significant correlation was observed between the microarray results and real-time RT-PCR analysis of 39 of these genes. Cluster analysis revealed 3 expression patterns, 29 transcripts of moderate abundance that were decreased (-93%) to very low levels, 106 transcripts that were downregulated (-42%), and 46 transcripts that were upregulated (+70%). Functional groups that were decreased included inflammatory response (-93%, n = 6), immune response (-86%, n = 7), and cytokines (-82%, n = 7). There was an overall upregulation in the oxidoreductase activity group (+47%, n = 9). Individually, six transcripts in this group were increased (+72%), and three were decreased (-34%). Fourteen of the genes map to regions in the rat genome that have been linked to increased blood pressure, and of 142 upstream regions analyzed, sequences resembling the DNA binding site for PPARgamma were identified in 101 of the differentially expressed genes.

Author List

Keen HL, Ryan MJ, Beyer A, Mathur S, Scheetz TE, Gackle BD, Faraci FM, Casavant TL, Sigmund CD

Authors

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Gene Expression Profiling
Gene Expression Regulation
Hypertension
Inflammation
Male
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Rats
Receptors, Cytoplasmic and Nuclear
Thiazolidinediones
Transcription Factors