Proteinase 3 Drives Murine Diabetic Kidney Disease by Mediating Caspase-3-dependent Apoptosis of Podocytes

Podocytes play a pivotal role in maintaining homeostasis of the glomerular filtration barrier. The underlying mechanism is unclear but podocyte loss represents a critical event that contributes to the development of diabetic kidney disease (DKD). Proteinase 3 (PR3) is a serine protease with selective high abundance in myeloid cells and pleiotropic effects on the regulation of innate immunity. Here, we demonstrate that PR3 abundance in the kidney was markedly increased, predominantly in podocytes, in a mouse model of DKD. Genetic ablation of PR3 significantly attenuated severe proteinuria, mesangial matrix expansion, and podocyte injury in diabetic mice. The present study aimed to investigate the role of PR3 in glomerular podocytes in DKD. Overall design: Comparative gene expression profiling analysis of RNA-seq data using renal glomeruli from PR3 KO and WT control mice with diabetic kidney disease