Administration of AGEs in vivo induces genes implicated in diabetic glomerulosclerosis.
Administration of advanced glycosylation end products (AGEs), prepared on mouse albumin, to normal young adult mice, resulted in an increase in mean glomerular volume and up-regulation of laminin B1 and alpha 1 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 occurring in the early stage of diabetic nephropathy, suggesting a participation of AGEs in these events.
Yang
C W
CW
Renal Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
Vlassara
H
H
Striker
G E
GE
Striker
L J
LJ
D000818:Animals; D002452:Cell Count; D003094:Collagen / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006984:Hypertrophy; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D006146:Guanidines; D007797:Laminin; D012333:RNA, Messenger; D012709:Serum Albumin; D003094:Collagen; C004479:pimagedine