ADVANCED GLYCATION END-PRODUCTS UP-REGULATE GENE-EXPRESSION FOUND IN DIABETIC GLOMERULAR-DISEASE

Several lines of evidence suggest that the excessive accumulation of e xtracellular matrix in the glomeruli of diabetic kidneys may be due to reactive intermediates forming between glucose and matrix proteins ca lled advanced glycation end products (AGEs). Normal mice received AGE- modified mouse serum albumin i.p. for 4 weeks, and glomerular extracel lular matrix, growth factor mRNA levels, and morphology were examined. We found that AGE induced an increase in glomerular extracellular mat rix alpha 1(IV) collagen, laminin B1, and transforming growth factor b eta(1) mRNA levels, as measured by competitive PCR, as well as glomeru lar hypertrophy. The AGE response was specific because the coadministr ation of an AGE inhibitor, aminoguanidine, reduced all these changes. We conclude that AGEs affected expression of genes implicated in diabe tic kidney disease and may play a major role in nephropathy.