Increased expression of the tight junction molecule claudin-18 A1 in both experimental colitis and ulcerative colitis.
BACKGROUND
We previously identified a major quantitative trait locus (qtl) on mouse chromosome 9 (Tnbs1) that confers resistance/susceptibility to trinitrobenzene sulfonic acid (TNBS) induced colitis. Here we wanted to identify possible candidate genes in this locus.


METHODS
We applied micro-array technology and identified claudin-18 as a plausible candidate gene in the Tnbs1 region. Subsequently we studied the expression profile of this gene by means of RT-PCR in resistant and susceptible mice as well as in human inflammatory bowel disease.


RESULTS
Expression of this gene was markedly upregulated during colitis in mice. Also in humans relative expression of claudin-18 in patients with ulcerative colitis was significantly upregulated as compared to healthy individuals undergoing surveillance endoscopy (n = 13, P < 0.0005). Expression was not related to the histological severity of the disease.


CONCLUSIONS
Claudins belong to the integral membrane proteins of the tight junction, a structure that seals off the intercellular space between adjacent epithelial cells and regulates passive diffusion of solutes and macromolecules. This study demonstrates for the first time that claudin-18 is expressed in human and mouse colon. Expression is upregulated during experimental colitis and in patients with ulcerative colitis. The observation that this is unrelated to the severity of inflammation might point to a primary defect in regulation in patients with ulcerative colitis and warrants further genetic examination.
Zwiers
Antonie
A
Department of Gastroenterology, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.
Fuss
Ivan J
IJ
Leijen
Suzanne
S
Mulder
Chris J
CJ
Kraal
Georg
G
Bouma
Gerd
G
D017398:Alternative Splicing; D000818:Animals; D057167:Claudins; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
C486683:CLDN18 protein, human; D057167:Claudins; C438899:Cldn18 protein, mouse; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid