H. Sakai et al., LOCALIZATION OF GLYCATED PROTEINS IN THE GLOMERULI OF PATIENTS WITH DIABETIC NEPHROPATHY, Nephrology, dialysis, transplantation, 11, 1996, pp. 66-71
Glycation of proteins is regarded as one of the major causes of the de
velopment and progression of diabetic nephropathy. Based on the numero
us reports on experimental models and on our own newly developed techn
iques, we planned to localize Amadori products and advanced glycation
end-products (AGEs), as well as the mRNA expression of cytokines, enzy
mes and their inhibitors, which are responsible for the expansion of t
he mesangial areas of the glomeruli. Ten patients with diabetic nephro
pathy were examined. Patients with immunoglobulin (Ig) A nephropathy a
nd normal portions of the surgically removed kidneys served as control
s. Amadori products and AGEs in biopsy specimens were stained by speci
fic monoclonal antibodies, and mRNA expression of the above substances
was detected by in situ hybridization. There was a parallel progressi
on in the degree of staining with anti-Amadori product antibody or ant
i-AGE antibody with the severity of tissue damage in patients with dia
betic nephropathy. Patients with IEA nephropathy and normal renal tiss
ues did not show any positive staining with these antibodies. The expr
ession of transforming growth factor beta 1, stromelysin and tissue in
hibitor of matrix proteinase 1 in the glomeruli was decreased in diabe
tic patients with advanced tissue damage, but they were progressively
expressed in the advanced stage of IEA nephropathy. It is concluded th
at Amadori products and of AGEs were formed in parallel in diabetic ki
dneys. The decrease in the expression of the cytokine and enzymes migh
t be due to altered protein formation associated with glycation.