DOI: 10.2337/diabetes.55.04.06.db05-0355 © 2006 by the American Diabetes Association ZO-1 Expression and Phosphorylation in Diabetic Nephropathy
1 South Texas Veterans Health Care System, San Antonio, Texas Address correspondence and reprint requests to Hernan Rincon-Choles, MD, University of Texas Health Science Center at San Antonio, Department of Medicine, Division of Nephrology, MSC 7882, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: choles{at}uthscsa.edu
Abbreviations:
ARB, angiotensin II receptor blocker; GEC, glomerular epithelial cell
Cellular mechanisms responsible for the loss of capillary wall permselectivity in diabetic nephropathy are not well characterized. ZO-1 is a junctional protein involved in the assembly and proper function of a number of tight junctions and is also expressed at the junction of podocytes with the slit diaphragm. We investigated the effect of diabetes and high glucose concentration on the expression of ZO-1 in animal models of both type 1 and 2 diabetes and in rat glomerular epithelial cells. In diabetic animals, immunohistochemistry and Western blotting showed decreased expression of ZO-1 in glomeruli. Immunogold electron microscopy revealed redistribution of ZO-1 from the podocyte membrane to the cytoplasm in the diabetic animals. Exposure of rat glomerular epithelial cells to high glucose resulted in a decrease in the intensity of ZO-1 staining and redistribution of ZO-1 from the membrane to the cytoplasm, changes that are attenuated by blockade of the angiotensin II type 1 receptor. ZO-1 protein expression and serine and tyrosine phosphorylation of ZO-1 were also decreased in cells exposed to high glucose. These findings suggest that alterations in the content and localization of ZO-1 may be relevant to the pathogenesis of proteinuria in diabetes.
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