Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease
Authors Ricanek P, Lunde L, Frye S, Stoen M, Nygård S, Morth J, Rydning A, Vatn M, Amiry-Moghaddam M, Tønjum T
Received 27 June 2014
Accepted for publication 15 September 2014
Published 9 January 2015 Volume 2015:8 Pages 49—67
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Andreas M Kaiser
Petr Ricanek,1,2 Lisa K Lunde,3 Stephan A Frye,1 Mari Støen,1 Ståle Nygård,4 Jens P Morth,5,6 Andreas Rydning,2 Morten H Vatn,7,8 Mahmood Amiry-Moghaddam,3 Tone Tønjum,1,9
1Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, 2Department of Gastroenterology, Akershus University Hospital, Lørenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 3Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 4Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, 5Centre for Molecular Medicine, Nordic EMBL Partnership, University of Oslo, 6Institute for Experimental Research, Oslo University Hospital (Ullevaal), Oslo, 7EpiGen Institute, Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 8Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, 9Department of Microbiology, University of Oslo, Oslo, Norway
Objectives: 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.
Conclusion: 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.
Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, aquaporins, aquaglyceroporins
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