VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway

作者：Guo, Jia; Lu, Congqun; Zhang, Fangxing; Yu, Haixia; Zhou, Mengwen; He, Meixia; Wang, Chunyan; Zhao, Zhanzheng; Liu, Zhangsuo^*

来源：Cellular Physiology and Biochemistry, 2017, 43(1): 39-51.

DOI：10.1159/000480315

• Diabetic nephropathy
• Proteinuria
• Podocytes
• Vitamin D receptor
• Paricalcitol
• Wnt signaling pathway

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease and proteinuria is one of the most prominent clinical manifestations. The expression of Vitamin D receptor (VDR) in patients with chronic kidney diseases was decreased, while VDR agonists could partially alleviate the proteinuria of DN in animal models. The present study was designed to determine the expression of VDR in renal tissues and its relationship with proteinuria the diabetic model db/db mice. Methods: The regulation effects of VDR on the Wnt signaling pathway were analyzed using RNA interference and VDR agonist paricalcitol. Results: With the increase in age of the db/db mice, the VDR protein and mRNA levels in renal tissues were decreased, proteinuria increased, and the protein and mRNA levels of GSK-3 beta of and beta-catenin increased. Paricalcitol treatment resulted in the up-regulation of VDR and down-regulation of GSK-3 beta and beta-catenin, indicating that VDR had a regulatory effect on the Wnt signaling pathway. Conclusion: VDR activation could reduce proteinuria of DN mice and alleviate high-glucose-induced injury of kidneys and podocytes by regulating the key molecules of Wnt signaling pathway.

• 单位
  河南省医药科学研究院; 郑州大学