The Mechanism of GPR39 Peptide Agonist in the Colonocyte Recovery

Abstract

GPR39 is an orphan GPCR that is highly expressed in the gastrointestinal tract and is known to be involved in epithelial recovery. In the recovery phase after the DSS-induced disease phase, Colon tissue without GPR39 showed a significantly lower regeneration of tight junction complex, proliferation of colon tissue, and colonic crypt structure than wild type. In the present study, we identified the role of GJ39A, GPR39 peptide agonist previously developed by my lab member, by investigating the effect of GPR39 on the colonocyte recovery upon GJ39A treatment. Activation of GPR39 by GJ39A triggered Gαq protein-mediated signaling, and it resulted in the intracellular influx of Ca2+ and increased phosphorylation of ERK. And GJ39A increased the mRNA expression of tight junction complex components, occludin, claudins-1, and ZO-1. Plus, GJ39A controlled the mRNA expression of cell cycle-related factors, p53, cyclin-dependent kinase (CDK) 4/6, increasing the proliferation of colonocyte. Taken together, GJ39A enhances epithelial barrier function and proliferation in colonocyte.