GSK-3β and Vitamin D Receptor are Involved in β-Catenin and Snail Signaling in High Glucose-Induced Epithelial-Mesenchymal Transition of Mouse Podocytes

Cellular Physiology and Biochemistry

关键词: Podocytes;    Epithelial-mesenchymal transition;    Glycogen synthase kinase 3β;    β-catenin;    Snail;    Diabetic nephropathy;   

DOI  :  10.1159/000358678

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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 3β (GSK-3β), β-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-3β, β-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. β-catenin and Snail pathways were assessed after down-regulating GSK-3β expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA). Results HG increased GSK-3β, β-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased α-SMA expression (mesenchymal marker). GSK-3β inhibitor and GSK-3β siRNA decreased β-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3β and β-catenin did not completely overlap; β-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced β-catenin nuclear translocation. Conclusion Down-regulating GSK-3β expression decreased β-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3β might be a target to slow or prevent DN.

【 授权许可】

CC BY-NC-ND