ZO-1 expression and phosphorylation in diabetic nephropathy

• Published in: Diabetes (New York, N.Y.) Vol. 55; no. 4; pp. 894 - 900
• Main Authors: RINCON-CHOLES, Hernan, VASYLYEVA, Tetyana L, PERGOLA, Pablo E, BHANDARI, Basant, BHANDARI, Kusum, ZHANG, Jian-Hua, WEN WANG, GORIN, Yves, BARNES, Jeffrey L, ABBOUD, Hanna E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2006
• Subjects: Animals; Antibodies; Biological and medical sciences; Blood Glucose - metabolism; Cell Membrane - metabolism; Creatinine; Cytoplasm - metabolism; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes research; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Diabetic neuropathies; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fluorides; Gene expression; Genetic aspects; Glucose; Kidney Cortex - metabolism; Kidneys; Laboratory animals; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Mice; Microscopy; Nephrology. Urinary tract diseases; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation; Podocytes - metabolism; Protein expression; Protein Transport; Proteins; Proteinuria; Rats; Rats, Sprague-Dawley; Urinary system involvement in other diseases. Miscellaneous; Urine; Zonula Occludens-1 Protein; Endocrinopathy; Kidney disease; Diabetic nephropathy; Phosphorylation; Urinary system disease; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.55.04.06.db05-0355

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.