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Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease

Yang, C.W., Vlassara, H., Peten, E.P., He, C.J., Striker, G.E., Striker, L.J.
Proceedings of the National Academy of Sciences of the United States of America 1994 v.91 no.20 pp. 9436-9440
messenger RNA, serum albumin, glomerulopathy, chemical reactions, glucose, diabetes mellitus, laminin, collagen, mice, gene expression, transforming growth factors, extracellular matrix
Several lines of evidence suggest that the excessive accumulation of extracellular matrix in the glomeruli of diabetic kidneys may be due to reactive intermediates forming between glucose and matrix proteins called advanced glycation end products (AGEs). Normal mice received AGE-modified mouse serum albumin i.p. for 4 weeks, and glomerular racellular matrix, growth factor mRNA levels, and morphology were examined. We found that AGE induced an increase in glomerular extracellular matrix alpha 1(IV) collagen, laminin B1, and transforming growth factor beta 1, mRNA levels, as measured by competitive PCR, as well as glomerular hypertrophy. The AGE response was specific because the coadministration of an AGE inhibitor, aminoguanidine, reduced all these changes. We conclude that AGEs affected expression of genes implicated in diabetic kidney disease and may play a major role in nephropathy.