Administration of AGEs in vivo induces genes implicated in diabetic glomerulosclerosis

Administration of advanced glycosylation end products (AGEs), prepared on mouse albumin, to normal yound adult mice, resulted in an increase in mean glomerular volume and up-regulation of laminin B1 and α1 type IV collagen mRNAs measured by competitive PCR in single microdissected glomeruli. Both glomerular hypertrophy and overexpression of genes coding for extracellular matrix were abrogated when aminoguanidine, an inhibitor of AGE cross-linking, was added to the AGEs injections, suggesting that the glomerular response to AGEs was specific. The effects of AGEs administration in vivo are comparable to those occuring in the early stage of diabetic nephropathy, suggesting a participation of AGEs in these events.