DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease
| Autor: | Annemarie Poustka, Gaby Bergmann, Arie V. Nieuw Amerongen, Vito Annese, Uffe Holmskov, Antoon J. M. Ligtenberg, Mauro D'Amato, Stefan Lyer, Inge Krebs, Frank Autschbach, Jens Madsen, Stephanie Blaich, Anna Latiano, Petra Kioschis, Floris J. Bikker, Rainer Wittig, Melanie Hudler, Sabine Gronert-Sum, Olga Strobel-Freidekind, Peter Schirmacher, Marcus Renner, Jan Mollenhauer, Caroline End, Burkhard Helmke, Nikolaus Gassler, Frank Hilberg, Axel Benner, Mathias Hafner |
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| Přispěvatelé: | Orale Biochemie (OUD, ACTA) |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent Nod2 Signaling Adaptor Protein Mice Transgenic Receptors Cell Surface Biology Inflammatory bowel disease Pathogenesis Mice Intestinal mucosa Crohn Disease Risk Factors NOD2 medicine Animals Humans RNA Messenger Colitis Intestinal Mucosa Child Aged Aged 80 and over Crohn's disease Hepatology Interleukin-6 Tumor Necrosis Factor-alpha Tumor Suppressor Proteins Calcium-Binding Proteins Dextran Sulfate Gastroenterology Mucins Exons Middle Aged medicine.disease Ulcerative colitis Crohn's Disease Activity Index digestive system diseases Up-Regulation DNA-Binding Proteins Case-Control Studies Immunology Female Disease Susceptibility Gene Deletion |
| Zdroj: | Renner, M, Bergmann, G, Krebs, I, End, C, Lyer, S, Hilberg, F, Helmke, B, Gassler, N, Autschbach, F, Bikker, F, Strobel-Freidekind, O, Gronert-Sum, S, Benner, A, Blaich, S, Wittig, R, Hudler, M, Ligtenberg, A J, Madsen, J, Holmskov, U, Annese, V, Latiano, A, Schirmacher, P, Amerongen, A V N, D'Amato, M, Kioschis, P, Hafner, M, Poustka, A & Mollenhauer, J 2007, ' DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease ', Gastroenterology, vol. 133, no. 5, pp. 1499-509 . https://doi.org/10.1053/j.gastro.2007.08.007 Gastroenterology, 133, 1499-1509. W.B. Saunders Ltd Renner, M, Bergmann, G, Krebs, I, End, C, Lyer, S, Hillberg, F, Helmke, B, Gassler, N, Autschbach, F, Bikker, F J, Strobel-Freidekind, O, Gronert-Sum, S, Benner, A, Blaich, S, Wittig, R, Hudler, M, Ligtenberg, A J M, Madsen, J, Holmskov, U, Annese, V, Latiano, A, Schirmacher, P, van Nieuw Amerongen, A, D'Amato, M, Kioschis, P, Hafner, M, Poustka, A & Mollenhauer, J 2007, ' DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease ', Gastroenterology, vol. 133, pp. 1499-1509 . https://doi.org/10.1053/j.gastro.2007.08.007 |
| ISSN: | 0016-5085 |
| Popis: | Udgivelsesdato: 2007-Nov BACKGROUND & AIMS: Impaired mucosal defense plays an important role in the pathogenesis of Crohn's disease (CD), one of the main subtypes of inflammatory bowel disease (IBD). Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein with predominant expression in the intestine and has been proposed to exert possible functions in regenerative processes and pathogen defense. Here, we aimed at analyzing the role of DMBT1 in IBD. METHODS: We studied DMBT1 expression in IBD and normal tissues by quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and mRNA in situ hybridization. Genetic polymorphisms within DMBT1 were analyzed in an Italian IBD case-control sample. Dmbt1(-/-) mice were generated, characterized, and analyzed for their susceptibility to dextran sulfate sodium-induced colitis. RESULTS: DMBT1 levels correlate with disease activity in inflamed IBD tissues. A highly significant fraction of the patients with IBD displayed up-regulation of DMBT1 specifically in the intestinal epithelial surface cells and Paneth cells. A deletion allele of DMBT1 with a reduced number of scavenger receptor cysteine-rich domain coding exons is associated with an increased risk of CD (P = .00056; odds ratio, 1.75) but not for ulcerative colitis. Dmbt1(-/-) mice display enhanced susceptibility to dextran sulfate sodium-induced colitis and elevated Tnf, Il6, and Nod2 expression levels during inflammation. CONCLUSIONS: DMBT1 may play a role in intestinal mucosal protection and prevention of inflammation. Impaired DMBT1 function may contribute to the pathogenesis of CD |
| Databáze: | OpenAIRE |
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