Gsk-3 Beta And Vitamin D Receptor Are Involved In Beta-Catenin And Snail Signaling In High Glucose-Induced Epithelial-Mesenchymal Transition Of Mouse Podocytes

Background: Epithelial-mesenchymal transition (EMT) is recognized to play an important role in diabetic nephropathy (DN). Objective: To analyze the roles of glycogen synthase kinase 3 beta (GSK-3 beta), beta-catenin and Snail signaling in high glucose (HG)-induced mouse podocytes EMT. Methods: Differentiated podocytes were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3 beta, beta-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. beta-catenin and Snail pathways were assessed after down-regulating GSK-3 beta expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA). Results: HG increased GSK-3 beta, beta-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased alpha-SMA expression (mesenchymal marker). GSK-3 beta inhibitor and GSK-3 beta siRNA decreased beta-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3 alpha and beta-catenin did not completely overlap; beta-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced beta-catenin nuclear translocation. Conclusion: Down-regulating GSK-3 beta expression decreased beta-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3 beta might be a target to slow or prevent DN. Copyright (C) 2014 S.Karger AG, Basel