Targeting Heparanase Attenuates Podocyte Injury Induced by Puromycin Aminonucleoside

Abstract

Podocytes are highly specialized glomerular visceral epithelial cells critical for maintaining the structure and function of the glomerular filtration barrier. These cells adhere to the glomerular basement membrane (GBM) and envelop the outer surfaces of the glomerular capillaries to prevent protein leakage during blood ultrafiltration. The GBM is a dense network of extracellular matrix composed of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. In this study, we investigated the protective effect of a heparanase inhibitor on puromycin aminonucleoside (PAN)-induced podocyte injury. Our results demonstrate that PAN treatment significantly disrupted the cytoskeletal architecture of cultured podocytes, reducing the formation of focal adhesions and stress fibers. Interdigitating intercellular junctions were replaced by dot-like structures with accumulated filamentous actin. Co-treatment with the heparanase inhibitor PI-88 effectively prevented these PAN-induced cytoskeletal abnormalities. Furthermore, a BSA filtration assay revealed that PI-88 attenuated PAN-induced increases in podocyte monolayer permeability. Taken together, our findings suggest that heparanase inhibition protects against podocyte injury and may represent a potential therapeutic strategy for glomerular diseases.