Gene expression profile after peroxisome proliferator activator receptor-gamma ligand administration in dextran sodium sulfate mice.
BACKGROUND
Peroxisome proliferator activator receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily. Ligands of PPARgamma, thiazolidione derivatives, have been reported to be the one of the candidates for the treatment of inflammatory bowel disease (IBD). Given the fact that PPARgamma is a transcription regulator, expression pharmacogenomics, including differential gene expression profiling of drug responses in a colitis model, is thought to be a useful approach for finding relevant genes that can serve as the target for new drug treatment of IBD.


METHODS
We performed a global analysis for differential gene expression of the intestine in a dextran sodium sulfate (DSS) colitis mouse model following PPARgamma ligand administration. By applying a high-density oligonucleotide array method, the expression patterns of approximately 12000 genes were analyzed, and selected genes were confirmed by a real-time quantitative PCR method.


RESULTS
The analysis of downregulated genes in the DSS mice following PPARgamma administration revealed several functional gene clusters with altered expression: (1) oncogene families such as GRO1 oncogenes, (2) inflammatory mediator-related genes such as the interferon-gamma gene, (3) water electrolyte-associated genes, and (4) others.


CONCLUSIONS
This is the first demonstration of global gene expression analysis using the DSS colitis mouse model with a PPARgamma ligand, and these results provide new insight for finding novel target genes for treating IBD.
Nakajima
Atsushi
A
Third Department of Internal Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Wada
Koichiro
K
Katayama
Kazufumi
K
Saubermann
Lawrence
L
Osawa
Emi
E
Nagase
Hajime
H
Ueno
Norio
N
Matsuhashi
Nobuyuki
N
Aburatani
Hiroyuki
H
D000818:Animals; D001483:Base Sequence; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000628:therapy*; D016264:Dextran Sulfate; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010597:Pharmacogenetics; D012333:RNA, Messenger / Q000032:analysis*; D018160:Receptors, Cytoplasmic and Nuclear; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000494:pharmacology*
D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016264:Dextran Sulfate