1. ¹Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Helsinki
2. ²Department of Medicine, Helsinki University Central Hospital and Minerva Institute for Medical Research, Helsinki
3. ³University of Turku, Turku, Finland

Correspondence: Dr. Harry Holthöfer, Senior Scientist of the Finnish Academy, Haartman Institute, Department of Bacteriology and Immunology, PB 21 (Haartmaninkatu 3), FIN-00014 University of Helsinki, Helsinki, Finland. E-mail: Harry.Holthofer@Helsinki.Fi

Received 29 November 2000.

Abstract

Diabetic nephropathy is a major complication of diabetes leading to thickening of the glomerular basement membrane, glomerular hypertrophy, mesangial expansion, and overt renal disease. The pathophysiologic mechanisms of diabetic nephropathy remain poorly understood. Nephrin is a recently found podocyte protein crucial for the interpodocyte slit membrane structure and maintenance of an intact filtration barrier. Here we have assessed the role of nephrin in two widely used animal models of diabetes, the streptozotocin model of the rat and the nonobese diabetic mouse. In both models, the expression levels of nephrin-specific mRNA as determined by real-time quantitative polymerase chain reaction increased up to two-fold during several weeks of follow-up. Immunohistochemical stainings revealed nephrin also more centrally within the glomerular tuft along with its preferential site in podocytes. Interestingly, as detected by immunoblotting, nephrin protein was also found in the urine of streptozotocin-induced rats. We conclude that nephrin is connected to the early changes of diabetic nephropathy and thus may contribute to the loss of glomerular filtration function.