Transcriptomics

Dataset Information

6

Interference with PPAR gamma signaling in mesenteric artery


ABSTRACT: Pharmacological activation of the transcription factor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. In contrast, naturally occurring mutations (e.g., P467L, V290M) in the ligand binding domain of PPAR gamma in humans leads to severe insulin resistance and early-onset hypertension. Experimental evidence, including whole genome expression profiling, suggests that these mutant versions of PPAR gamma act in a dominant negative manner. Because PPAR gamma is expressed in a variety of cell types and tissues, we generated a transgenic mouse model (SP467L) specifically targeting dominant negative PPAR gamma to the vascular smooth muscle cells in order to determine the action of PPAR gamma in the blood vessel independent of its systemic metabolic actions. In the data set provided herein, we examined the gene expression profile in mesenteric vessels from SP467L mice and their control littermates using the Affymetrix mouse exon 1.0 ST array. We generated transgenic mice specifically targeting expression of mutant dominant negative human PPAR gamma (P467L) to vascular smooth muscle using a smooth muscle-specific promoter (smooth muscle myosin heavy chain or SMMHC). Mesenteric arteries were isolated from 3 male transgenic mice and 4 non-transgenic littermate controls. Total RNA was prepared using conventional methods and quality was assessed using the Bioanalyzer 2100 (Agilent Technologies). For the microarray hybridizations, each sample corresponded to mesenteric artery derived from one mouse. All procedures were conducted at the University of Iowa DNA Core facility using standard Affymetrix protocols. In brief, approximately 50 ng of total RNA was used as input to a two-step amplification procedure (NuGen, http://www.nugeninc.com/) to generate biotin-labeled RNA fragments for hybridization to the Affymetrix mouse exon 1.0 ST array.

ORGANISM(S): Mus musculus  

SUBMITTER: Henry L Keen   Curt D Sigmund  Henry Keen 

PROVIDER: E-GEOD-36482 | ArrayExpress | 2012-09-24

SECONDARY ACCESSION(S): GSE36482PRJNA153519

REPOSITORIES: GEO, ArrayExpress

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Publications

PPARγ regulates resistance vessel tone through a mechanism involving RGS5-mediated control of protein kinase C and BKCa channel activity.

Ketsawatsomkron Pimonrat P   Lorca Ramón A RA   Keen Henry L HL   Weatherford Eric T ET   Liu Xuebo X   Pelham Christopher J CJ   Grobe Justin L JL   Faraci Frank M FM   England Sarah K SK   Sigmund Curt D CD  

Circulation research 20120907 11


Activation of peroxisome proliferator-activated receptor-γ (PPARγ) by thiazolidinediones lowers blood pressure, whereas PPARγ mutations cause hypertension. Previous studies suggest these effects may be mediated through the vasculature, but the underlying mechanisms remain unclear.To identify PPARγ mechanisms and transcriptional targets in vascular smooth muscle and their role in regulating resistance artery tone.We studied mesenteric artery (MA) from transgenic mice expressing dominant-negative  ...[more]

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