The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype.
OBJECTIVE
Recent studies have suggested that an increased intestinal permeability is involved in the pathophysilogy of irritable bowel syndrome (IBS). However, the differential expression of tight junctions (TJs) proteins according to IBS subtypes and symptoms remained unknown. The objective of this study was to study zonula occludens-1 (ZO-1), occludin, and claudin-1 in the colonic mucosa of patients with IBS.


METHODS
Fifty IBS patients fulfilling the Rome III criteria and 31 controls were included. All types of IBS patients participated with predominant diarrhea (IBS-D, n=19), predominant constipation (IBS-C, n=14), constipation alternating with diarrhea (IBS-A, n=15), or unclassified (IBS-U, n=2). IBS symptom intensity was quantified on 10-cm Visual Analog Scale (VAS). TJ proteins (claudin-1, ZO-1, occludin) were quantified by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), western blot, while their localization was determined by immunofluorescence.


RESULTS
ZO-1 and occludin expression was lower in IBS patients compared with controls, whereas only a trend for a decrease of claudin-1 was observed. The mRNA levels remained unaffected. In the subgroup analyses, occludin and claudin-1 expression was decreased in IBS-D patients but not in IBS-C and IBS-A patients. The subcellular distribution of these three proteins was altered in IBS-C and IBS-D patients. Occludin (r=0.40, P<0.01) and claudin-1 (r=0.46, P<0.01) expression was correlated with the duration of symptoms. The expression of occludin was lower in patients with an abdominal pain intensity higher than 6 on the VAS (P<0.05).


CONCLUSIONS
Occludin and claudin-1 appeared markedly affected in IBS-D patients. In addition, our results suggest that alteration of TJ proteins may be involved in the initiation of IBS and contribute to visceral hypersensitivity.
Department of Gastroenterology, Rouen University Hospital, France.
Nathalie
N
Bertiaux-Vandaële
Stéphanie Beutheu
SB
Youmba
Liliana
L
Belmonte
Stéphane
S
Lecleire
Michel
M
Antonietti
Guillaume
G
Gourcerol
Anne-Marie
AM
Leroi
Pierre
P
Déchelotte
Jean-François
JF
Ménard
Philippe
P
Ducrotté
Moïse
M
Coëffier
D015746:Abdominal Pain / Q000503:physiopathology; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D062445:Claudin-1; D003106:Colon / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D062793:Occludin; D010147:Pain Measurement; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011795:Surveys and Questionnaires; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
C568108:CLDN1 protein, human; D062445:Claudin-1; D017931:DNA Primers; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein