EFFECTS OF GLYCATED ALBUMIN ON MESANGIAL CELLS - EVIDENCE FOR A ROLE IN DIABETIC NEPHROPATHY

被引:73
作者
ZIYADEH, FN
COHEN, MP
机构
[1] UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104
[2] UNIV PENN,DEPT BIOCHEM,PHILADELPHIA,PA 19104
[3] UNIV PENN,PENN CTR MOLEC STUDIES KIDNEY DIS,PHILADELPHIA,PA 19104
关键词
DIABETIC NEPHROPATHY; GLYCATED ALBUMIN; MESANGIAL CELLS; NONENZYMATIC GLYCATION;
D O I
10.1007/BF00926830
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nonenzymatically glycated proteins are preferentially transported across the glomerular filtration barrier, and the glomerular mesangium in diabetes is bathed with serum containing increased concentrations of glycated albumin. We investigated effects of glycated albumin on mesangial cells, which are involved in diabetic nephropathy. [H-3]-thymidine incorporation was significantly inhibited when murine mesangial cells were grown in culture media containing human serum that had been nonenzymatically glycated by incubation for 4 days with 28 mM glucose. This inhibition was reversed when monoclonal antibodies that selectively react with Amadori products of glycated albumin were added to the culture media. Purified glycated albumin containing Amadori adducts of the glycation reaction induced significant inhibition of thymidine incorporation and stimulation of Type IV collagen secretion compared with cells cultured in the presence of purified nonglycated albumin. These changes were prevented when monoclonal antibodies specifically reactive with fructosyl-lysine epitopes in glycated albumin were added to the cultures. The antibodies had no effect on growth or collagen production in the presence of nonglycated albumin. The results provide the first evidence directly implicating Amadori adducts in glycated albumin in the pathogenesis of diabetic nephropathy, which is characterized by decreased cellularity in association with expansion of the mesangial matrix.
引用
收藏
页码:19 / 25
页数:7
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