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

被引:35
作者
Guo, Jia [1 ,2 ,3 ]
Lu, Congqun [1 ,2 ,3 ]
Zhang, Fangxing [1 ,2 ,3 ]
Yu, Haixia [1 ,2 ,3 ]
Zhou, Mengwen [1 ,2 ,3 ]
He, Meixia [4 ]
Wang, Chunyan [1 ,2 ,3 ]
Zhao, Zhanzheng [1 ,2 ,3 ]
Liu, Zhangsuo [1 ,2 ,3 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Nephrol Ctr, Zhengzhou, Henan, Peoples R China
[2] Zhengzhou Univ, Inst Nephrol, Zhengzhou, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Inst Clin Med, Zhengzhou, Henan, Peoples R China
[4] Zhengzhou Univ, Henan Acad Med & Pharmaceut Sci, Zhengzhou, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Diabetic nephropathy; Proteinuria; Podocytes; Vitamin D receptor; Paricalcitol; Wnt signaling pathway; VITAMIN-D-RECEPTOR; DIABETIC-NEPHROPATHY; MESENCHYMAL TRANSITION; DISEASE PATIENTS; BETA-CATENIN; DYSFUNCTION; CELLS; METAANALYSIS; ALBUMINURIA; INHIBITION;
D O I
10.1159/000480315
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (C) 2017 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:39 / 51
页数:13
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