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EXPRESSION PROFILING OF FIVE RAT STRAINS REVEAL TRANSCRIPTIONAL MODES IN THE ANTIGEN PROCESSING PATHWAY
Citation:
WARD, W. O., M. SCHLADWEILER, A. D. LEDBETTER, AND U. P. KODAVANTI. EXPRESSION PROFILING OF FIVE RAT STRAINS REVEAL TRANSCRIPTIONAL MODES IN THE ANTIGEN PROCESSING PATHWAY. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
We hypothesized that co-transcribed, intra-pathway, functionally coherent genes can be revealed from analysis of microarray data from ozone-exposed rat strains.
Description:
Comparative gene expression profiling of rat strains with genetic predisposition to diverse cardiovascular diseases can help decode the transcriptional program that governs cellular behavior. We hypothesized that co-transcribed, intra-pathway, functionally coherent genes can be revealed from analysis of microarray data from ozone-exposed rat strains. Male 12-14 wks old Wistar Kyoto (WKY, healthy), Spontaneously Hypertensive (SHR), Stroke-Prone SHR (SHRSP), Heart Failure SHR (SHHF) and Diabetic (JCR) rats were exposed to air or ozone (l ppm) for 4 hrs. At the conclusion of the exposure period, lung tissue was extracted and analyzed for gene expression using rat 230A Affymetrix GeneChips. Principal component analysis of the 10 experimental conditions demonstrated remarkable strain-related and ozone-treatment induced differences in gene expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified from 9 to 22 pathways differentially expressed in these rat strains regardless of ozone (p<0.05 by hypergeometric test of over-represented differentially expressed genes). One of the pathways with more significantly altered genes, the antigen processing pathway of SHHF, was chosen for further analysis. For the thirty genes comprising this pathway a correlation matrix across the ten experimental conditions (both air and ozone combined) was computed. Amazingly there were only two groups of co-transcribed genes. The first group consisted primarily of MHC class II processing genes and the second group was comprised primarily of inflammation and acute phase response mediating genes. In addition the first group was upregulated in the strains with likely healthy immune systems, WKY and JCR; whereas, the second group was upregulated in strains with compromised immune systems, SHHF, SHR and SHRSP. Thus, the transcribed modules were related to the immune competence of the respective strains. We believe this type of analysis may reveal transcription modules with functionally cohesive genes that express unique disease phenotypes or toxic responses to environmental exposures.