Skip to main content
Log in

Gene expression profile after peroxisome proliferator activator receptor-γ ligand administration in dextran sodium sulfate mice

  • Biotherapy and biological response modifiers for IBD
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background. Peroxisome proliferator activator receptor-gamma (PPARγ) is a member of the nuclear receptor superfamily. Ligands of PPARγ, thiazolidione derivatives, have been reported to be the one of the candidates for the treatment of inflammatory bowel disease (IBD). Given the fact that PPARγ 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 PPARγ 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 PPARγ 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 PPARγ ligand, and these results provide new insight for finding novel target genes for treating IBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. vanDullemen HM, vanDeventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995;109:129–35.

    Article  PubMed  Google Scholar 

  2. Lawrance IC, Fiocchi C, Chakravarti S. Ulcerative colitis and Crohn’s disease: distinctive gene expression profiles and novel susceptibility candidate genes. Hum Mol Genet 2001;10:445–56.

    Article  PubMed  CAS  Google Scholar 

  3. Uthoff SM, Eichenberger MR, Lewis RK, Fox MP, Hamilton CJ, McAuliffe TL, et al. Identification of candidate genes in ulcerative colitis and Crohn’s disease using cDNA array technology. Int J Oncol 2001;19:803–10.

    PubMed  CAS  Google Scholar 

  4. Dieckgraefe BK, Stenson WF, Korzenik JR, Swanson PE, Harrington CA. Analysis of mucosal gene expression in inflammatory bowel disease by parallel oligonucleotide arrays. Physiol Genomics 2000;4:1–11.

    PubMed  CAS  Google Scholar 

  5. Gelman L, Fruchart JC, Auwerx J. An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer. Cell Mol Life Sci 1999;55:932.

    Article  PubMed  CAS  Google Scholar 

  6. Kersten S, Wahli W. Peroxisome proliferator activated receptor agonists. EXS (Basel) 2000;89:141.

    CAS  Google Scholar 

  7. Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000; 49:497.

    Article  PubMed  CAS  Google Scholar 

  8. Nakajima A, Wada K, Miki H, Kubota N, Nakajima N, Terauchi Y, et al. Endogenous PPAR gamma mediates anti-inflammatory activity in murine ischemia-reperfusion injury. Gastroenterology 2001;120:460–9.

    Article  PubMed  CAS  Google Scholar 

  9. Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, et al. Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Cancer Res 2002;62:233–40.

    PubMed  CAS  Google Scholar 

  10. Saubermann LJ, Beck P, DeJong YP, Pitman RS, Ryan MS, Kim HS, et al. Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology 2000;119:11–6.

    Article  Google Scholar 

  11. Hippo Y, Yashiro M, Ishii M, Taniguchi H, Tsutsumi S, Hirakawa K, et al. Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res 2001;61:889–95.

    PubMed  CAS  Google Scholar 

  12. Rajeevan MS, Ranamukhaarachchi DG, Vernon SD, Unger ER. Use of real-time quantitative PCR to validate the results of cDNA array and differential display PCR technologies. Methods (Orlando) 2001;25:443–51.

    CAS  Google Scholar 

  13. Ierardi E, Principi M, Francavilla R, Passaro S, Noviello F, Burattini O, Francavilla A. Epithelial proliferation and ras p21 oncoprotein expression in rectal mucosa of patients with ulcerative colitis. Dig Dis Sci 2001;46:1083–7.

    Article  PubMed  CAS  Google Scholar 

  14. Lang SM, Heinzlmann M, Stratakis DF, Teschauer W, Loeschke K. Detection of Ki-ras mutations by PCR and differential hybridization and of p53 mutations by SSCP analysis in endoscopically obtained lavage solution from patients with long-standing ulcerative colitis. Am J Gastroenterol 1997;92:2166–70.

    PubMed  CAS  Google Scholar 

  15. Bisping G, Lugering N, Lutke-Brintrup S, Pauels HG, Schurmann G, Domschke W, Kucharzik T. Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells. Clin Exp Immunol 2001;123:15–22.

    Article  PubMed  CAS  Google Scholar 

  16. Salomon P, Pizzimenti A, Panja A, Reisman A, Mayer L. The expression and regulation of class II antigens in normal and inflammatory bowel disease peripheral blood monocytes and intestinal epithelium. Autoimmunity 1991;9:141–9.

    Article  PubMed  CAS  Google Scholar 

  17. Turtzo LC, Lee MD, Lu M, Smith BL, Copeland NG, Gilbert DJ, et al. Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a candidate mutant phenotype, ataxia. Genomics 1997;41:267–70.

    Article  PubMed  CAS  Google Scholar 

  18. Narushima Y, Unno M, Nakagawara K, Mori M, Miyashita H, Suzuki Y, et al. Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIII alpha, RegIII beta, RegIII gamma. Gene (Amst) 1997;185:159–68.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakajima, A., Wada, K., Katayama, K. et al. Gene expression profile after peroxisome proliferator activator receptor-γ ligand administration in dextran sodium sulfate mice. J Gastroenterol 37 (Suppl 14), 62–66 (2002). https://doi.org/10.1007/BF03326416

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03326416

Keywords

Navigation