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Enteroendocrine cells in terminal ileal Crohn's disease.
MedLine Citation:
PMID:  22398079     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: Enteroendocrine cells sense gut luminal contents, and orchestrate digestive physiology whilst contributing to mucosal homeostasis and innate immunity. The terminal ileum is the key site of EEC expression but detailed assessment of their subtypes, lineage transcription factors and expression products has not been undertaken in terminal ileal Crohn's disease. Recent Crohn's disease gene wide association studies have linked the neuroendocrine transcription factor Phox2b; while autoantibodies to an enteroendocrine protein, ubiquitination protein 4a, have been identified as a disease behaviour biomarker. METHODS: Terminal ileal tissue from small or large bowel Crohn's disease and normal controls was analysed for enteroendocrine marker expression by immunohistochemistry and quantitative polymerase chain reaction. Inflammation was graded by endoscopic, clinical, histological and biochemical scoring. RESULTS: In small bowel disease, glucagon-like peptide 1 and chromogranin A cells were increased 2.5-fold (p=0.049) and 2-fold (p=0.031) respectively. Polypeptide YY cells were unchanged. Ileal enteroendocrine cell expression was unaffected in the presence of Crohn's colitis. Phox2b was co-localised to enteroendocrine cells and showed a 1.5-fold increase in ileal disease. Significant mRNA increases were noted for chromogranin A (3.3-fold; p=0.009), glucagon-like peptide 1 (3.1-fold; p=0.007) and ubiquitination protein 4a (2.2-fold; p=0.02). Neurogenin 3, an enteroendocrine transcription factor showed ~2 fold-upregulation (p=0.048). CONCLUSIONS: Enhanced enteroendocrine cell activity is present in small bowel disease, and observed in restricted cell lineages. This may impact on the epithelial immune response, cellular homeostasis and nutrient handling and influence appetite via increased satiety signalling in the gut-brain axis.
Authors:
Gordon W Moran; Joanne Pennock; John T McLaughlin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-3
Journal Detail:
Title:  Journal of Crohn's & colitis     Volume:  -     ISSN:  1876-4479     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101318676     Medline TA:  J Crohns Colitis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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