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Glutathione peroxidase 2 and aquaporin 8 as new markers for colonic inflammation in experimental colitis and inflammatory bowel diseases: an important role for H2O2?

te Velde, Anje A.a; Pronk, Ingea; de Kort, Floora; Stokkers, Pieter C.F.b

European Journal of Gastroenterology & Hepatology: June 2008 - Volume 20 - Issue 6 - p 555-560
doi: 10.1097/MEG.0b013e3282f45751
Original Articles: Inflammatory Bowel Disease

Objective Different mouse models of inflammatory bowel diseases (IBD) demonstrate various aspects of the pathophysiology of IBD. We looked for overlapping gene expression profiles in three different mouse models of experimental colitis and analysed whether these overlapping genes are of help to find new genes that could be used as general markers in human IBD.

Methods Using Agilent mouse TOX oligonucleotide microarrays, we analysed the gene expression profiles in three widely used models of experimental colitis: 2,4,6-trinitrobenzene sulphonic acid, dextran sodium sulfate and CD4+CD45RBhigh transfer and looked for overlapping gene expression in these models. Overlapping genes were analysed using Lightcycler (Roche Diagnostics, Mannheim, Germany) in biopsy materials from human IBD and control tissue.

Results Compared with control mice in dextran sodium sulfate, 2,4,6-trinitrobenzene sulphonic acid and the CD45RB transfer colitis mice five known genes, extracellular proteinase inhibitor (Expi), glutathione peroxidase 2 (Gpx2), mast cell protease 1 (Mcpt1), resistin-like β (Retnlb) and sulphatase 2 (Sulf2), and two unknown genes were upregulated and the two genes aquaporin 8 (Aqp8) and kallikrein 5 (Klk5) were downregulated in all three models. In human Crohn's disease and ulcerative colitis biopsies, one of the upregulated glutathione peroxidase (Gpx2) and one of the downregulated Aqp8 genes in the mouse models were also differentially expressed in affected colonic tissue of patients with IBD.

Conclusion Experimental mouse models are suitable models for the search of new markers for human IBD. As both Gpx2 and Aqp8 are involved in H2O2 metabolism (Gpx2 as a radical scavenger whereas Aqp8 facilitates its diffusion), upregulation of Gpx2 and downregulation of Aqp8 could be a mechanism to defend against severe oxidative stress and indicate that H2O2 is a universal mediator in the inflammatory process in the colon. This provides a focus on homeostasis of the antioxidant pathway and its importance in IBD.

aCenter for Experimental and Molecular Medicine

bDepartment of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands

Correspondence to Dr Anje A. te Velde, PhD, Center for Experimental and Molecular Medicine H2-256, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands

Tel: +31 20 5662368; fax: +31 20 6977192;


Note: these data were presented previously at the DDW 2007, Washington, USA and published as an abstract in Gastroenterology 2007; 132:A557.

Received 6 June 2007 Accepted 26 September 2007

© 2008 Lippincott Williams & Wilkins, Inc.