Research on Correlation Between Psychological Factors, Mast Cells, and PAR-2 Signal Pathway in Irritable Bowel syndrome

J Inflamm Res. 2021 Apr 14:14:1427-1436. doi: 10.2147/JIR.S300513. eCollection 2021.


Purpose: The study aimed to explore the level of psychological stress factors, mast cell (MC), and neuropeptide in the occurrence of irritable bowel syndrome (IBS) and the correlation among them, and to identify representative and effective indicators for the pathogenesis and clinical medication development of IBS.

Subjects and methods: Twenty-eight patients (20-64 years old) with diarrhea-predominant IBS (IBS-D) were included in the IBS-D group and 8 healthy subjects (35-63 years old) were enrolled in the control group. All subjects accepted the colonoscopic biopsies, self-rating depression scale (SDS) and self-rating anxiety scale (SAS) assessment. MC degranulation, neuropeptide S (NPS), neuropeptide Y (NPY), NPY receptor 2 (NPY2R) and Protease-activated receptor 2 (PAR-2) in colon tissues were performed by Strept Avidin-Biot complex (SABC) immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) detection was used to test the expression of NPS and NPY in peripheral blood plasma and colon tissues. Western blot was applied to examine the level of NPY2R and PAR-2.

Results: The level of anxiety and depression of patients with IBS-D was more serious than that in the control. The expression of NPS, NPY and NPY2R was down-regulated in the IBS-D. The total MC and tryptase-positive MC increased significantly in the colon tissue of IBS-D and the expression level of PAR-2 was significantly up-regulated.

Conclusion: There has been a close connection among those indicators that the activated MC may up-regulate the function of PAR-2, resulting in the change of neuropeptide (NPS and NPY), successively leading to clinical symptoms and psychological negative changes in the IBS.

Keywords: Irritable bowel syndrome; diarrhea; mast cell; neuropeptide; protease-activated receptor 2.

Grants and funding

This research was supported by the National Natural Science Foundation of China (82074214, 81973598, 81573760), Zhejiang Provincial Natural Science Foundation of China (LY18H030001, LY16H030010), Medicine and Health Science and Technology Plan Projects in Zhejiang province (2017KY413), Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (2017ZA089, 2016ZB071, 2015ZZ012, 2014ZA030) and Medical Health Platform Plan Projects of Zhejiang Province (2015RCA020).