Journal of Molecular Medicine

, Volume 84, Issue 12, pp 1055–1066

Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease

Authors

  • Christoph Moehle
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
  • Nikolaus Ackermann
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
    • Institute of Internal Medicine IVUniversity of Heidelberg
  • Thomas Langmann
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
  • Charalampos Aslanidis
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
  • Alexander Kel
    • BIOBASE GmbH
  • Olga Kel-Margoulis
    • BIOBASE GmbH
  • Anna Schmitz-Madry
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
  • Alexandra Zahn
    • Institute of Internal Medicine IVUniversity of Heidelberg
  • Wolfgang Stremmel
    • Institute of Internal Medicine IVUniversity of Heidelberg
    • Institut für Klinische Chemie und LaboratoriumsmedizinUniversitätsklinikum Regensburg
Original Article

DOI: 10.1007/s00109-006-0100-2

Cite this article as:
Moehle, C., Ackermann, N., Langmann, T. et al. J Mol Med (2006) 84: 1055. doi:10.1007/s00109-006-0100-2

Abstract

Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelial barrier function in this disease. Therefore, ileal and colonic mucosal biopsies from nonaffected regions of patients with ulcerative colitis (UC) and Crohn’s disease (CD), as well as non-IBD probands, were subjected to Affymetrix DNA-microarray analysis. Real-time reverse transcription polymerase chain reaction was used for verification in larger IBD sample numbers. Disturbed mRNA expression was identified for several mucin genes in both disease groups and tissues. A significant downregulation in the colon was obtained for MUC2 in CD and MUC12 in CD and UC. Expression analysis of all dysregulated mucins in a broad human tissue panel revealed dominant epithelial tissue-specific transcription. In silico analysis of the regulatory regions of these mucins indicated nuclear factor κB (NFκB) binding sites in each promoter. Furthermore, NFκB was overrepresented in mucin promoters and a component of a specific combination of transcription factors (composite module). In vivo stimulation experiments in the adenocarcinoma cell line LS174T showed inducible mucin expression by the cytokines tumor necrosis factor-α and transforming growth factor-β, which could be blocked by NFκB signaling inhibitors. Allelic discrimination screening obtained statistically significant associations for the MUC2–V116M (P = 0.003) polymorphism with CD and for MUC4–A585S (P = 0.025), as well as MUC13–R502S (P = 0.0003) with UC. These data suggest that the disturbed expression of mucin genes and the connection to the NFκB pathway may influence the integrity of the intestine and therefore contribute to the pathophysiology of IBD.

Keywords

Inflammatory bowel diseaseMucinsDNA-microarrayReal-time RT-PCRAllelic discrimination

Supplementary material

109_2006_100_MOESM1_ESM.pdf (1.7 mb)
ESM Table 1Composite Module analysis result of human promoters. Displayed are the scores of each TF matrix and the overall composite score. (PDF 1815 kb)
109_2006_100_MOESM2_ESM.pdf (59 kb)
ESM Fig. 1(PDF 59 kb)

Copyright information

© Springer-Verlag 2006