G Protein–Coupled Receptor 35 Suppresses Oxidative Stress Responsive Kinase 1 in Diabetic Wound Healing

Endothelial cell dysfunction is a crucial feature of diabetic wound healing. The underlying molecular mechanisms are poorly understood. We investigated how G protein-coupled receptor 35 (GPR35) inhibition accelerates diabetic wound healing. We found that GPR35 modulated endothelial cell behavior in vitro and identified oxidative stress responsive 1 as its target. Inhibiting GPR35 rescued the healing process in animals with hyperglycemia. This study uncovers novel molecular mechanisms underlying the benefit of GPR35 inhibition on endothelial cell angiogenesis and provides proof-of-concept evidence for therapeutic strategies targeting GPR35 in the endothelium as a potential therapy for diabetic wound care.