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Open Access Research article

Whole-genome microarray analysis and functional characterization reveal distinct gene expression profiles and patterns in two mouse models of ileal inflammation

Leela Rani Avula1, Dries Knapen24, Roeland Buckinx1, Lucia Vergauwen2, Dirk Adriaensen1, Luc Van Nassauw13 and Jean-Pierre Timmermans1*

Author Affiliations

1 Department of Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium

2 Department of Biology, Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium

3 Faculty of Medicine and Health Sciences, Laboratory of Human Anatomy and Embryology, University of Antwerp, Groenenborgerlaan 171, Antwerp, B-2020, Belgium

4 Department of Veterinary Sciences, Laboratory of Physiology and Biochemistry of Domestic Animals, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium

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BMC Genomics 2012, 13:377  doi:10.1186/1471-2164-13-377

Published: 6 August 2012

Abstract

Background

Although a number of intestinal inflammatory conditions pertain to the ileum, whole-genome gene expression analyses in animal models of ileal inflammation are lacking to date. Therefore, we aimed to identify and characterize alterations in gene expression in the acutely inflamed ileum of two murine models of intestinal inflammation, namely intestinal schistosomiasis and TNBS-induced ileitis, compared to healthy controls. To this end, we used whole-genome microarrays, followed by bioinformatics analyses to detect over-represented Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology categories.

Results

Following screening of almost all known mouse genes and transcripts represented on the array, intestinal schistosomiasis and TNBS-induced ileitis yielded 207 and 1417 differentially expressed genes, respectively, with only 30 overlapping concordantly changed genes. Functional category groups consisting of complement and coagulation cascades, extracellular matrix (ECM)-receptor interaction, Fc epsilon receptor I signaling pathways and protein activation cascade, cell adhesion categories were over-represented in the differential gene list of intestinal schistosomiasis. Antigen processing and presentation, cell adhesion molecules, ABC transporters, Toll-like receptor signaling pathways and response to chemical stimulus categories were over-represented in the differential gene list of TNBS-induced ileitis. Although cytokine-cytokine receptor interaction, intestinal immune network for IgA production, focal adhesion pathways and immune, inflammatory and defense response categories were over-represented in the differential gene lists of both inflammation models, the vast majority of the associated genes and changes were unique to each model.

Conclusions

This study characterized two models of ileal inflammation at a whole-genome level and outlined distinct gene expression profiles and patterns in the two models. The results indicate that intestinal schistosomiasis involves Th2 responses, complement activation, protein activation and enhanced ECM turnover, while TNBS-induced ileitis involves Th17 responses, defective antigen processing and presentation and altered Toll-like receptor-mediated responses. Signs of an impaired epithelial barrier are apparent in both inflammation models. Furthermore, the comprehensive differential gene list and functional groups provided by this study constitute an interesting starting point to explore new targets and extended functional networks dealing with small bowel inflammation.

Keywords:
Gene expression; Intestinal inflammation; Ileum; Murine models; Intestinal schistosomiasis; TNBS-induced ileitis; Whole-genome microarrays; Pathways; Over-representation analysis