Aims/hypothesis: Changes in kidney function in diabetes could be due to changes in the kidney basement membranes. Proteoglycans are important constituents of this kidney extracellular matrix. This study explored the possibility that advanced glycation end products affect proteoglycan synthesis in cultured kidney epithelial cells.
Methods: Madin Darby Canine Kidney (MDCK) epithelial cells were cultured with either low glucose (5 mmol/l), low glucose with 10 micrograms/ml of N epsilon-(carboxymethyl)lysine bovine serum albumin (CML-BSA) or high glucose (25 mmol/l). From day 7-8 cells were labelled with either [35S]sulphate or [3H]glucosamine for 24 h. Labelled macromolecules were purified by gel and ion exchange chromatography, and isolated proteoglycans analysed by gel chromatography 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 diabetes patients CML-BSA, decreases proteoglycan expression in kidney epithelial cells. Advanced glycation end products could, accordingly, promote pathological changes in kidneys of diabetics.