The AGE product N-epsilon-(carboxymethyl)lysine serum albumin is a modulator of proteoglycan expression in polarized cultured kidney epithelial cells

Aims/hypothesis. Changes in kidney function in diabetes could be due to cha nges in the kidney basement membranes. Proteoglycans are important constitu ents of this kidney extracellular matrix. This study explored the possibili ty that advanced glycation end products affect proteoglycan synthesis in cu ltured kidney epithelial cells. Methods. Madin Darby Canine Kidney (MDCK) epithelial cells were cultured wi th either low glucose (5 mmol/l), low glucose with 10 mug/ml of N-epsilon-( carboxymethyl)lysine bovine serum albumin (CML-BSA) or high glucose (25 mmo l/l). From day 7-8 cells were labelled with either [S-35]sulphate or [H-3]g lucosamine for 24 h. Labelled macromolecules were were purified by gel and ion exchange chromatography, and isolated proteoglycans analysed by gel chr omatography and electrophoresis. Results. The CML- BSA treatment reduced the proteoglycan synthesis in MDCK cells. Neither the type of glycosaminoglycan chains made nor the molecular size of the chains was affected. Conclusion/interpretation. At concentrations found in the plasma of diabete s patients CML-BSA, decreases proteoglycan expression in kidney epithelial cells. Advanced glycation end products could, accordingly, promote patholog ical changes in kidneys of diabetics.