Glycated Albumin Stimulates Fibronectin and Collagen IV Production by Glomerular Endothelial Cells under Normoglycemic Conditions

Abstract

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates the synthesis of matrix by renal glomerular mesangial cells and has been causally linked to the pathogenesis of diabetic nephropathy. However, the effect of glycated albumin on the biology of glomerular endothelial cells, which elaborate a basement membrane that undergoes thickening in diabetes, has not been investigated. We used well-characterized rat glomerular endothelial cells to examine the influence of glycated albumin on the synthesis of extracellular matrix proteins by these cells in culture. Concentrations of glycated albumin that are present in clinical specimens stimulate fibronectin and collagen IV production by glomerular endothelial cells, and this effect is operative under normoglycemic conditions. These results support the hypothesis that increased glycated albumin contributes to glomerular basement membrane thickening in diabetes.