title: Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease.
abstract: OBJECTIVE
  The aim of this study was to investigate the relationship between aquaporin (AQP) water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD) in humans.
  
  
  METHODS
  Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA) levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-dimensional structures of AQP1, 3, 7, and 8 were modeled.
  
  
  RESULTS
  AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn's disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function.
  
  
  CONCLUSIONS
  AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is significantly reduced in patients with IBD, and they are differentially expressed in specific bowel segments in patients with Crohn's disease and ulcerative colitis. The data present a link between gut inflammation and water/solute homeostasis, suggesting that AQPs may play a significant role in IBD pathophysiology.
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway ; Department of Gastroenterology, Akershus University Hospital, Lørenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, Norway.
authors.forename: Petr
authors.initials: P
authors.lastname: Ricanek
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Lunde
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Frye
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Støen
authors.affiliation: Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, Norway.
authors.forename: Ståle
authors.initials: S
authors.lastname: Nygård
authors.affiliation: Centre for Molecular Medicine, Nordic EMBL Partnership, University of Oslo, Norway ; Institute for Experimental Research, Oslo University Hospital (Ullevaal), Oslo, Norway.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Morth
authors.affiliation: Department of Gastroenterology, Akershus University Hospital, Lørenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, Norway.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rydning
authors.affiliation: EpiGen Institute, Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, Norway ; Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Morten H
authors.initials: MH
authors.lastname: Vatn
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Amiry-Moghaddam
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway ; Department of Microbiology, University of Oslo, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Tønjum
keywords: Crohn’s disease; aquaglyceroporins; aquaporins; inflammatory bowel disease; ulcerative colitis