BACKGROUND: Irritable bowel syndrome (IBS) pathophysiology has not been fully understood. Abnormalities of serine proteases have been identified in IBS patients. In addition, protease-activated receptors (PAR) activation interferes with several components of the pathogenesis of IBS, so, evaluating the PAR expression in IBS patients may contribute to understanding the pathogenesis of the disease. AIMS: This study aimed to investigate whether the expression of PAR4 and PAR2 in the colon was changed in IBS patients and was associated with IBS. METHODS: Colon mucosal biopsies of 34 IBS patients (16 constipation- and 18 diarrhea-predominant) and 18 control subjects were collected. Gene transcripts of PAR2, PAR4, tryptase, and trypsin were quantified using real-time polymerase chain reaction (PCR) and the expression of PAR2 and PAR4 receptors was also measured by immunohistology and image analysis. RESULTS: In IBS patients, the mRNA expression of tryptase and trypsin normalized against β-actin gene was higher compared to control subjects (P < 0.001). No difference was observed in the PAR2 mRNA level or protein level between control subjects on the one hand and IBS patients or subgroups on the other. In IBS or IBS subgroups patients, the expression of PAR4 in the mRNA level or protein level was lower than the control subjects. CONCLUSIONS: This study, for the first time, indicated the PAR4 expression in IBS patients. Decreased PAR4 expression may help us to understand the pathogenesis of IBS.
BACKGROUND:Irritable bowel syndrome (IBS) pathophysiology has not been fully understood. Abnormalities of serine proteases have been identified in IBSpatients. In addition, protease-activated receptors (PAR) activation interferes with several components of the pathogenesis of IBS, so, evaluating the PAR expression in IBSpatients may contribute to understanding the pathogenesis of the disease. AIMS: This study aimed to investigate whether the expression of PAR4 and PAR2 in the colon was changed in IBSpatients and was associated with IBS. METHODS: Colon mucosal biopsies of 34 IBSpatients (16 constipation- and 18 diarrhea-predominant) and 18 control subjects were collected. Gene transcripts of PAR2, PAR4, tryptase, and trypsin were quantified using real-time polymerase chain reaction (PCR) and the expression of PAR2 and PAR4 receptors was also measured by immunohistology and image analysis. RESULTS: In IBSpatients, the mRNA expression of tryptase and trypsin normalized against β-actin gene was higher compared to control subjects (P < 0.001). No difference was observed in the PAR2 mRNA level or protein level between control subjects on the one hand and IBSpatients or subgroups on the other. In IBS or IBS subgroups patients, the expression of PAR4 in the mRNA level or protein level was lower than the control subjects. CONCLUSIONS: This study, for the first time, indicated the PAR4 expression in IBSpatients. Decreased PAR4 expression may help us to understand the pathogenesis of IBS.
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