Martínez, Cristina; Lobo, Beatriz; Pigrau, Marc; Ramos, Laura; González-Castro, Ana Maria; Alonso, Carmen; Guilarte, Mar; Guilá, Meritxell; de Torres, Ines; Azpiroz, Fernando; Santos, Javier; Vicario, María
Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier
Teil von
  • Gut, 2013-08, Vol.62 (8), p.1160-1168
Ort / Verlag
LONDON: BMJ Publishing Group Ltd and British Society of Gastroenterology
Links zum Volltext
Web of Science
Objective Recently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the intercellular apical junction complex (AJC) were expressed differently than in healthy subjects. The aim of the authors here was to determine whether these alterations are associated with structural abnormalities in AJC and their relationship with mast cell activation and IBS-D clinical manifestations. Design A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45) and healthy subjects (n=30). Mucosal mast cell number and activation were determined by quantifying CD117+ cells/hpf and tryptase expression, respectively. Expression and distribution of AJC specific proteins were evaluated by western blot and confocal microscopy. AJC ultrastructure was assessed by transmission electron microscopy. Results Compared with healthy subjects, IBS-D patients exhibited: (a) increased mast cell counts and activation; (b) increased protein expression of claudin-2, reduced occludin phosphorylation and enhanced redistribution from the membrane to the cytoplasm; and (c) increased myosin kinase expression, reduced myosin phosphatase and, consequently, enhanced phosphorylation of myosin. These molecular alterations were associated with ultrastructural abnormalities at the AJC, specifically, perijunctional cytoskeleton condensation and enlarged apical intercellular distance. Moreover, AJC structural alterations positively correlated both with mast cell activation and clinical symptoms. Conclusion The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. These results provide evidence for the organic nature of IBS-D, a heretofore model disease of functional gastrointestinal disorders.
ISSN: 0017-5749
ISSN: 1468-3288
DOI: 10.1136/gutjnl-2012-302093
Links zum Inhalt
Abdomen, Abridged Index Medicus, Adolescent, Adult, anorectal function, antibacterial mucosal immunity, Biopsy, brain–gut interaction, Cell activation, Cell number, Confocal microscopy, Cytoplasm, Cytoskeleton, Diarrhea, Diarrhea - etiology, Diarrhea - metabolism, Diarrhea - pathology, Disease, enteric bacterial microflora, Female, functional bowel disorder, gas physiology, Gastroenterology, Gastroenterology & Hepatology, gastrointestinal motility, Gastrointestinal tract diseases, Gene expression, gut immunology, gut inflammation, Humans, Hypotheses, IBS-D, Inflammation, Intercellular Junctions - ultrastructure, intestinal barrier function, intestinal mast cells, Intestinal Mucosa - metabolism, Intestinal Mucosa - pathology, Intestinal Mucosa - ultrastructure, intestinal permeability, Intestine, Irritable bowel syndrome, Irritable Bowel Syndrome - complications, Irritable Bowel Syndrome - metabolism, Irritable Bowel Syndrome - pathology, Jejunum - metabolism, Jejunum - pathology, Jejunum - ultrastructure, Kinases, Life Sciences & Biomedicine, Lymphocytes B, Male, Mast cells, Mast Cells - pathology, Middle Aged, motility disorders, Mucosa, mucosal mast cells, Myosin, Myosin Light Chains - metabolism, neural–immune interactions, neurogastroenterology, Pain, Permeability, Phosphorylation, Prospective Studies, Proteins, Rodents, Science & Technology, serotonin, Sex Factors, small bowel disease, Small intestine, stress, Stress, Psychological - complications, Studies, Tight Junction Proteins - metabolism, tight junction signalling, Transmission electron microscopy, Tryptase, Ultrastructure, visceral sensitivity, Young Adult

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