Complement C5a/C5a receptor 1 induces renal injury in diabetic kidney disease via mitochondrial metabolic reprogramming

In mice, complement C5a and its receptor C5aR1 elicit systemic and local inflammation and drive tissue injury in diabetic kidney disease via altered metabolic flexibility, which can be attenuated by therapy with a specific orally active inhibitor of C5aR1. Overall design: Bulk RNA-seq was performed to understand gene expression changes in the mouse kidney due to diabetes and treatment with a C5a inhibitor (oral). There were four sample groups (1) non-diabetic mice given the vehicle; (2) STZ diabetic mice given the vehicle; (3) non-diabetic mice given C5a inhibitor PMX-53; and (4) STZ diabetic mice given the C5a inhibitor PMX-53.