Moehle, Christoph and Ackermann, Nikolaus and Langmann, Thomas and Aslanidis, Charalampos and Kel, Alexander and Kel-Margoullis, Olga and Schmitz-Madry, Anna and Zahn, Alexandra and Stremmel, Wolfgang and Schmitz, Gerd (2006) Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. JOURNAL OF MOLECULAR MEDICINE-JMM, 84 (12). pp. 1055-1066. ISSN 0946-2716, 1432-1440
Full text not available from this repository. (Request a copy)Abstract
Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (1131)). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelia] 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 down-regulation 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 kappa B (NF kappa B) binding sites in each promoter. Furthermore, NF kappa B 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-a and transforming growth factor-beta, which could be blocked by NF kappa B 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 NF kappa B pathway may influence the integrity of the intestine and therefore contribute to the pathophysiology of IBD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; GENOME-WIDE SEARCH; COLON-CANCER CELLS; ULCERATIVE-COLITIS; CROHNS-DISEASE; MOLECULAR-CLONING; PROMINENT MUCIN; TRANSCRIPTION; SUSCEPTIBILITY; IDENTIFICATION; inflammatory bowel disease; mucins; DNA-microarray; real-time RT-PCR; allelic discrimination |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jan 2021 09:27 |
| Last Modified: | 18 Jan 2021 09:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33705 |
Actions (login required)
 |
View Item |
