Proteinase 3 Drives Murine Diabetic Kidney Disease by Mediating Caspase-3-dependent Apoptosis of Podocytes - PubMed
6 hours ago
- #Diabetic Kidney Disease
- #Proteinase 3
- #Podocyte Apoptosis
- Proteinase 3 (PR3) is identified as a key mediator in murine diabetic kidney disease (DKD), driving podocyte apoptosis via caspase-3 activation.
- Podocyte-specific PR3 knockout mice showed reduced proteinuria, mesangial matrix expansion, and podocyte injury in DKD models.
- High glucose conditions increased PR3 levels and activity in podocytes, leading to caspase-3 cleavage and apoptosis, which was mitigated by PR3 inhibition.
- Overexpression of PR3 in podocytes exacerbated caspase-3 cleavage and apoptosis, while PR3 deficiency protected against podocyte injury.
- Therapeutic intervention with elafin, a serine protease inhibitor, attenuated podocyte loss and DKD progression in mice, suggesting a potential treatment strategy.