Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis.
OBJECTIVE
To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease (IBD).


METHODS
To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis (UC) and Crohn's disease (CD) compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed.


RESULTS
We could show that aquaporin-8 (AQP8) mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQP8, however, revealed no mutations or polymorphisms in IBD patients.


CONCLUSIONS
Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflammation and ulceration.
Zahn
Alexandra
A
Department of Gastroenterology, University Hospital of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. alexandra.zahn@med.uni-heidelberg.de
Moehle
Christoph
C
Langmann
Thomas
T
Ehehalt
Robert
R
Autschbach
Frank
F
Stremmel
Wolfgang
W
Schmitz
Gerd
G
D000328:Adult; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000209:etiology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020346:Aquaporins; D012333:RNA, Messenger; C108330:aquaporin 8