JOURNAL ARTICLE

GSK-3β and vitamin D receptor are involved in β-catenin and snail signaling in high glucose-induced epithelial-mesenchymal transition of mouse podocytes

Jia Guo, Nannan Xia, Lili Yang, Sijie Zhou, Qian Zhang, Yingjin Qiao, Zhangsuo Liu
Cellular Physiology and Biochemistry 2014, 33 (4): 1087-96
24732862

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. © 2014 S. Karger AG, Basel.

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