In recent years, the Wnt/β-catenin signaling has gained tremendous attention due to its ability to modulate a number of diseases including diabetic nephropathy. Studies have shown that there is decrease in the secretion of Wnt proteins including Wnt4, 5a and Wnt 6 during high glucose concentration or diabetic conditions, which leads to decreased translocation of β-catenin to nucleus. The down-regulation of Wnt/β-catenin signaling leads to detrimental effects on kidney including increased apoptosis of mesangial cells and increased deposition of fibrous tissue in mesangium. The pharmacological modulators such as spironolactone, NO donor and antioxidant are shown to produce beneficial effects in diabetic nephropathy by up regulating the expression of Wnt proteins and activation of diabetes-induced suppressed Wnt/β-catenin signaling. On the other hand, it is documented that diabetes leads to overactivation of Wnt1/β-catenin signaling, which promotes podocyte injury, induce epithelial-mesenchymal transition of podocytes along with renal injury and fibrosis. Accordingly, different interventions aimed to suppress overactivated Wnt/β-catenin signaling are reported to improve the condition and symptoms associated with diabetic nephropathy. The present review discusses the dual role of Wnt/beta-catenin signaling in the pathogenesis of diabetic nephropathy.
Keywords: Beta-Catenin; Diabetes; Kidney; Nephropathy; Oxidative stress; Wnt.
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