Heparanase-1 Gene Expression and Regulation by High Glucose in Renal Epithelial Cells A Potential Role in the Pathogenesis of Proteinuria in Diabetic Patients

glycan downregulation in the glomerular basement membrane (GBM) of the kidneys with diabetic nephrop-athy remain controversial. In the present study, we showed that the expression of heparanase-1 (HPR1), a heparan sulfate–degrading endoglycosidase, was up-regulated in the renal epithelial cells in the kidney with diabetic nephropathy. Urinary HPR1 levels were ele-vated in patients with diabetic nephropathy. In vitro cell culture studies revealed that HPR1 promoter– driven luciferase reporter gene expression, HPR1 mRNA, and protein were upregulated in renal epithelial cells under high glucose conditions. Induction of HPR1 expression by high glucose led to decreased cell surface heparan sulfate expression. HPR1 inhibitors were able to restore cell surface heparan sulfate expression