The Role and Mechanism of PAR2 Gene Knockout on IBS Colon Motility

Abstract

Background: It has previously been shown that protease-activated receptor 2 (PAR2) could be involved in regulating the visceral hypersensitivity process. It has also been shown that PAR2 expression in the intestinal tissue of a visceral hypersensitivity rat model was increased and that the activation of intestinal PAR2 significantly increased the intestinal sensitivity of rats. Based on that, the research reported here aimed to explore the role and mechanism of PAR2 on the colonic motility regulating progress in an irritable bowel syndrome (IBS) rat model via Nesfatin-1. Methods: Neonatal two days old male Sprague Dawley PAR2^+/+ and PAR2^-/- rats were randomized into control and IBS model groups. IBS syndrome model rats were made via the method of mother-infant separation and acetic acid enema. After successful verification, rats were divided into control, PAR2^+/+IBS, PAR2^-/-IBS, PAR2^-/-IBS with central intervention, and PAR2^-/-IBS with peripheral intervention groups. The colonic motility indexes and the colonic tissues mammalian target of rapamycin (mTOR) expression of rats were collected and the statistical differences of various groups were determined. Results: (1) The abdominal withdraw reflex (AWR) scores of PAR2^+/+IBS model group (WM group) and PAR2^-/- IBS model group (KM group) were higher than control group (C group), and the WM group score was the highest (p < 0.05). The colonic histological staining of the WM and KM groups all excluded organic pathological changes. PAR2^+/+ and PAR2^-/-IBS models were successfully established. (2) The amplitude and frequency of the colonic fast wave in the KM+ Nesfatin-1 central intervention group (KM+NCI group) were higher than in the WM, KM, and KM+Nesfatin-1 peripheral intervention groups (KM+NPI groups) (p < 0.05). The KM group was the lowest. The amplitude and frequency of colonic slow wave in the KM+NCI group were higher than in the WM, KM and KM+Nesfatin-1 peripheral intervention groups (KM+NPI groups, p < 0.05). The KM group was the lowest. (3) Colonic mTOR expression in the KM+NCI group was higher than in the WM, KM and KM+NPI groups (p < 0.05). The highest colonic mTOR expression was in the KM+NCI group, the lowest expression was in the KM group. Conclusions: The PAR2 gene knockout affected the Nesfatin-1 central and peripheral pathways of regulating IBS colonic motility and mTOR expression. It was speculated that Nesfatin-1 might regulate IBS colonic motility through the PAR2/mTOR signaling pathway with Nesfatin-1 central intervention method and Nesfatin-1 peripheral intervention method.