Increased Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Diabetic Rat Glomeruli: Glomerular Hyperfiltration Is a Potential Mechanism of ICAM-1 Upregulation

作者：Hikaru Sugimoto, Kenichi Shikata, Kyoji Hirata, Kenji Akiyama, Mitsuhiro Matsuda, Masahiko Kushiro, Yasushi Shikata, Nobuyuki Miyatake, Masayuki Miyasaka, Hirofumi Makino · 发表于：Diabetes · 年份：1997 · DOI：10.2337/diab.46.12.2075 · 被引用次数：189 · 研究领域：Cell Adhesion Molecules Research、Diabetes Treatment and Management、Fibroblast Growth Factor Research

Mononuclear cells, including monocytes/macrophages and T-cells, are considered to be involved in the progression of diabetic nephropathy, although the mechanism of their recruitment into diabetic glomeruli is unclear. The intercellular adhesion molecule-1 (ICAM-1) promotes the infiltration of leukocytes into atherosclerotic lesions as well as inflammatory tissues. In the present study, we investigated the expression of ICAM-1 in the glomeruli of streptozotocin-induced diabetic rats. The expression of ICAM-1 was increased significantly during the early stage of diabetes. The number of mononuclear cells, primarily monocytes/macrophages and lymphocytes, was significantly increased in diabetic glomeruli. Mononuclear cell infiltration into diabetic glomeruli was prevented by anti-ICAM-1 monoclonal antibody. Insulin treatment decreased ICAM-1 expression and mononuclear cell infiltration. The ICAM-1 expression on cultured human umbilical vein endothelial cells was not induced under high glucose culture conditions. Glomerular hyperfiltration is a characteristic change in the early stage of diabetic nephropathy. Treatment with aldose reductase inhibitor, which prevented glomerular hyperfiltration without changes in blood glucose levels, decreased ICAM-1 expression and mononuclear cell infiltration. Moreover, we examined the ICAM-1 expression in the glomeruli of the 5/6 nephrectomized rat, which is a model for glomerular hyperfiltration without hyperglycemia. The ICAM-1 expression and ...