Published online Mar 28, 2020. doi: 10.3748/wjg.v26.i12.1242
Peer-review started: October 17, 2019
First decision: November 22, 2019
Revised: January 18, 2020
Accepted: March 5, 2020
Article in press: March 5, 2020
Published online: March 28, 2020
Inflammatory bowel disease (IBD) is a complex disease with multiple pathogenic factors. Although the pathogenesis of IBD is still unclear, a current hypothesis suggests that genetic susceptibility, environmental factors, a dysfunctional immune system, the microbiome, and the interactions of these factors substantially contribute to the occurrence and development of IBD. Although existing and emerging drugs have been proven to be effective in treating IBD, none can cure IBD permanently. G protein-coupled receptors (GPCRs) are critical signaling molecules implicated in the immune response, cell proliferation, inflammation regulation and intestinal barrier maintenance. Breakthroughs in the understanding of the structures and functions of GPCRs have provided a driving force for exploring the roles of GPCRs in the pathogenesis of diseases, thereby leading to the development of GPCR-targeted medication. To date, a number of GPCRs have been shown to be associated with IBD, significantly advancing the drug discovery process for IBD. The associations between GPCRs and disease activity, disease severity, and disease phenotypes have also paved new avenues for the precise management of patients with IBD. In this review, we mainly focus on the roles of the most studied proton-sensing GPCRs, cannabinoid receptors, and estrogen-related GPCRs in the pathogenesis of IBD and their potential clinical values in IBD and some other diseases.
Core tip: Inflammatory bowel disease is a complex and heterogeneous disease with unclear pathogenesis. Advances in the understanding of the structures and functions of G protein-coupled receptors (GPCRs) have been a driving force for exploring the roles of GPCRs in the pathogenesis of diseases, thereby leading to the development of GPCR-targeted medication. In this review, we mainly focus on the roles of GPCRs in the pathogenesis of inflammatory bowel disease and their potential values in disease diagnosis, treatment and monitoring.