Rabbit Anti-Human GPR31 (a.a. 121-220) Polyclonal antibody

Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE production inhibits IR-induced liver dysfunction, inflammation and cell death in mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model that closely recapitulates clinical liver dysfunction following liver resection. Most strikingly, blocking 12-HETE accumulation effectively attenuated all pathologies of hepatic IR in this model. Collectively, this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE- GPR31 axis that functionally determines hepatic IR procession. We have also provided proof of concept that blocking 12-HETE production is a promising strategy for preventing and treating IR-induced liver damage.

The G protein-coupled receptors (GPCRs) constitute a large superfamily of seven transmembrane-spanning receptors that are activated by several classes of ligands, including bioactive lipids. GPCRs are attractive therapeutic targets for the treatment of human diseases, as they finely regulate a wide array of cellular functions. In this minireview, we summarized what is currently known about the G protein-coupled receptor GPR31/12-HETER. We highlighted, in particular, its structural similarity with human homologs, the biological functions of its recognized ligand 12(S)-hydroxyeicosatetraenoic acid (HETE), an arachidonic acid metabolite, and the role that GPR31/12-HETER-mediated signals play in cancer cell growth, invasion and metastasis, and in liver ischemia-reperfusion (IR) injury. Recent studies shed light and interest on the 12(S)-HETE/GPR31/12-HETER-activated signaling pathways and functions. The full spectrum of GPR31/12-HETER-mediated biological functions has yet to be characterized. Further studies are needed to identify other potential ligands, i.e. other than 12(S)-HETE. Another important remaining question is whether the multiple 12(S)-HETE-induced biological activities, including its role in diabetes, neurodegeneration, neuroprotection, and platelet function, occur via GPR31/12-HETER and/or involve the activation of other receptor molecules and pathways.