LOCALIZATION OF GLYCATED PROTEINS IN THE GLOMERULI OF PATIENTS WITH DIABETIC NEPHROPATHY

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.