Podocyte-directed VEGFC gene therapy prevents increased glomerular permeability and glycocalyx damage in experimental type 1 diabetes.

ABSTRACT: Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, and current interventions fail to directly target the glomerulus, where the disease initiates. Vascular endothelial growth factor (VEGF)C is a key contributor to glomerular endothelial barrier function. In transgenic mice, podocyte-specific overexpression of human VEGFC was protective in early DKD. Here, we investigated the therapeutic potential of a podocyte-targeted VEGFC gene therapy in DKD. We employed an adeno-associated virus (AAV2/9) to drive human VEGFC in human and mouse podocytes. Expressed VEGFC was functional in vitro. In type 1 diabetic mice (induced by streptozotocin), systemic administration of AAV2/9 increased glomerular human VEGFC expression, ameliorating both albuminuria and increased glomerul

SUBMITTER: Martin Alonso A 

PROVIDER: S-EPMC12925785 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature