Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease.
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 extracellular 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.
Yang
C W
CW
Renal Cell Biology Section, Metabolic Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Vlassara
H
H
Peten
E P
EP
He
C J
CJ
Striker
G E
GE
Striker
L J
LJ
D000199:Actins / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D017931:DNA Primers; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D007797:Laminin / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D016133:Polymerase Chain Reaction / Q000379:methods; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000199:Actins; D017931:DNA Primers; D017127:Glycation End Products, Advanced; D007797:Laminin; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D003094:Collagen