Z Gastroenterol 2010; 48 - A22
DOI: 10.1055/s-0030-1254760

Correlation of disease severity in ulcerative colitis with fecal MMP-9 levels, occludin, PAR-2 and PAR-4 mRNA expression in corresponding biopsies

K Gecse 1, A Annaházi 1, V Bezirard 2, M Leveque 2, A Rosztóczy 1, R Róka 1, F Izbéki 1, T Molnár 1, F Nagy 1, L Ferrier 2, L Bueno 2, T Wittmann 1
  • 1First Department of Internal Medicine, University of Szeged, Szeged, Hungary
  • 2UMR 1054 INRA/EI-Purpan NGN Unit, Toulouse, France

Introduction: Active ulcerative colitis (UC) is characterized by tight junction alterations and increased gut permeability. Matrix-metalloprotease 9 (MMP-9) is capable of occludin degradation and disruption of the epithelial barrier, while increased PAR-2 promoter methylation was shown in patients with severe forms of the disease. Our aims were: 1. to examine the correlation of UC disease severity with fecal levels of MMP-9 and occludin mRNA and protein expression; 2. to examine PAR-2 and 4 mRNA expressions related to disease severity.

Methods: 14 UC patients and 6 control subjects undergoing colonoscopy were involved in the study. In UC patients, disease severity was evaluated by the Mayo score, and biopsies originated from inflamed areas of the rectal mucosa. MMP-9 was measured by enzyme linked immunosorbant assay in the fecal samples, while western blotting was used to determine occludin protein expression and qPCR to measure occludin, PAR-2 and 4 mRNA levels in the biopsies.

Results: MMP-9 was undetectable in the feces of control subjects, however its level was slightly elevated in patients with low Mayo scores (LM group; 8.2±4.1ng/mg prot) and significantly elevated in patients with more severe activity (HM group; 24.2±5.7; p<0.05). In parallel, occludin protein and mRNA levels were slightly decreased in the LM group (93.8±45.7%), and significantly decreased at the HM group (17.0±9.7%) compared to controls (191.8±61.9%). Similarly, PAR-2 mRNA levels were significantly decreased only in biopsies of UC patients in the HM group compared to controls (605.4±142.3 vs. 1121±63.25, p<0.05). On the contrary, PAR-4 mRNA levels were elevated in the HM group, compared to controls (498.5±178.4 vs. 63.69±51.20).

Conclusions: MMP-9 is detectable only in the feces of UC patients, and its level depends upon disease severity, while occludin protein and its mRNA level diminish in the same group of patients. In severe UC PAR-2 mRNA is reduced, while PAR-4 mRNA is overexpressed in concordance with disease severity.