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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 20; pp. 9436 - 9440
• Main Authors: Yang, Chih-Wei, Vlassara, Helen, Peten, Emmanuel P., He, Ci-Jiang, Striker, Gary E., Striker, Liliane J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 27.09.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Actins - biosynthesis; albuminas; albumine; albumins; Amino Acid Sequence; Animals; arn mensajero; arn messager; blood proteins; chemical reactions; colagenos; collagen; Collagen - biosynthesis; collagene; Collagens; Complementary DNA; diabete; Diabetes; Diabetes complications; Diabetic nephropathies; Diabetic Nephropathies - metabolism; DNA Primers; enfermedades renales; expresion genica; expression des genes; Female; gene expression; Gene Expression Regulation - drug effects; Genes; genetica; genetics; genetique; Glomerulus; glucosa; glucose; Glycation End Products, Advanced - pharmacology; Kidney - metabolism; kidney diseases; Kidney Glomerulus - metabolism; Kidneys; Laminin - biosynthesis; Medical disorders; Medical research; Messenger RNA; Mice; Mice, Inbred Strains; Molecular Sequence Data; nephropathie; peptide; peptides; peptidos; Platelet-Derived Growth Factor - biosynthesis; Polymerase chain reaction; Polymerase Chain Reaction - methods; proteinas sanguineas; proteine sanguine; raton; reacciones quimicas; reaction chimique; rein; rinones; Serum Albumin, Bovine - pharmacology; souris; Transforming Growth Factor beta - biosynthesis; Type 1 diabetes mellitus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.20.9436

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.