Supported by the National Institutes of Health grants R21AI069027 (to C.S.K.) and R21AI076956 (to S.B.) and a Crohn's & Colitis Foundation of America Senior Research Award (to C.S.K.).
Multifactorial patterns of gene expression in colonic epithelial cells predict disease phenotypes in experimental colitis†
Article first published online: 22 FEB 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 11, pages 2138–2148, November 2012
How to Cite
Frantz, A. L., Bruno, M. E.C., Rogier, E. W., Tuna, H., Cohen, D. A., Bondada, S., Chelvarajan, R. L., Brandon, J. A., Jennings, C. D. and Kaetzel, C. S. (2012), Multifactorial patterns of gene expression in colonic epithelial cells predict disease phenotypes in experimental colitis. Inflamm Bowel Dis, 18: 2138–2148. doi: 10.1002/ibd.22923
- Issue published online: 15 OCT 2012
- Article first published online: 22 FEB 2012
- Manuscript Accepted: 27 JAN 2012
- Manuscript Received: 13 JAN 2012
- colonic epithelial cell;
- polymeric immunoglobulin receptor;
- experimental colitis;
- inflammatory bowel disease;
- gene expression;
The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.
We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. Factor analysis was used to combine the five biomarkers into two multifactorial principal components (PCs). PC scores for individual mice were correlated with disease severity.
For both colitis models, PC1 was strongly weighted toward RelA, A20, and pIgR, and PC2 was strongly weighted toward TNF and MIP-2, while the contributions of other biomarkers varied depending on the etiology of inflammation. Disease severity was correlated with elevated PC2 scores in DSS colitis and reduced PC1 scores in T-cell transfer colitis. Downregulation of pIgR was a common feature observed in both colitis models and was associated with altered cellular localization of pIgR and failure to transport IgA.
A multifactorial analysis of epithelial gene expression may be more informative than examining single gene responses in IBD. These results provide insight into the homeostatic and proinflammatory functions of CEC in IBD pathogenesis and suggest that biomarker analysis could be useful for evaluating therapeutic options for IBD patients. (Inflamm Bowel Dis 2012;)