The role of OXGR1 on gut smooth muscle to regulate intestinal motility and health

Abstract

Abstract Background A stable intestinal microenvironment determines the balance of intestinal flora and body health, which is influenced by intestinal motility. 2-Oxoglutarate receptor 1 (OXGR1) is a G-protein-coupled receptor whose endogenous ligand is the resistance exercise metabolic intermediate α-ketoglutarate (AKG). Here, we aimed to determine the function of OXGR1 in intestinal motility, which modulate intestinal microenvironment. Results Through intestinal co-location, we found OXGR1 was highly expressed in intestinal smooth muscle. The model of OXGR1 lose-of-function mice showed enhanced intestinal barrier and motility, as well as improved intestinal flora. We further found that in gastrointestinal smooth muscle cells (GSMCs), AKG downregulates Car2 expression and modulates cellular acid-base balance by OXGR1, ultimately leading to the relaxation and reduction of motility of intestinal smooth muscle. Conclusions OXGR1 deletion improves intestinal microenvironment by enhanced intestinal motility; and these results provide a new target for intestinal motility regulation, OXGR1 may be developed for the treatment of some diseases such as microbiota disorders and enteritis.