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

Abstract

Objectives: 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.