Grpr-flox Mouse

Grpr, the Gastrin-releasing Peptide Receptor, is a Gαq -coupling neuropeptide receptor belonging to the G protein-coupled receptors (GPCRs) family [2]. It binds to ligands like gastrin-releasing peptide (GRP) and is involved in multiple biological processes. The GRP/GRPR signalling is part of various pathophysiological pathways, including those related to inflammatory, cardiovascular, neurological diseases, and cancers [2].

In alcohol-associated liver injury (ALI), Grpr -/- and Grprflox/floxLysMCre mice showed alleviated ethanol-induced liver injury with reduced steatosis, lower levels of serum markers, decreased neutrophil influx, and reduced inflammatory cytokines release, indicating that GRPR enhances ALI through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway [1]. In hyperuricemia-induced renal inflammation and fibrosis, GRPR knockout or conditional knockout in renal tubular epithelial cells significantly alleviated renal function decline and fibrosis in HN mice, as GRP/GRPR promoted HN by suppressing the ABCG2/PDZK1 and increasing TGF-β/Smad3 levels via the NF-κB pathway [3]. Also, in acute kidney injury (AKI), genetic deletion of GRPR protected mice from cisplatin-and ischemia-induced AKI, and GRPR interacted with Toll-like receptor 4 to activate STAT1, which induced tubular epithelial cell necroptosis, necroinflammation, and macrophages recruitment [4].

In conclusion, Grpr plays a crucial role in multiple disease-related biological processes. Gene knockout and conditional knockout mouse models have revealed its pathogenic roles in ALI, hyperuricemia-induced renal injury, and AKI. These findings suggest that targeting Grpr could potentially be a therapeutic strategy for these diseases.