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Article

Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway

  • Authors:
    • Feng Gao
    • Min Yao
    • Yanping Cao
    • Shuxia Liu
    • Qingjuan Liu
    • Huijun Duan
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Biochemistry, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
  • Pages: 1328-1336
    |
    Published online on: March 11, 2016
       https://doi.org/10.3892/ijmm.2016.2525
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Abstract

The Notch pathway is known to be linked to diabetic nephropathy (DN); however, its underlying mechanism was poorly understood. In the present study, we examined the effect of Valsartan, an angiotensin II type 1 receptor antagonist, on the Notch pathway and podocyte loss in DN. Diabetes was induced in mice by an intraperitoneal injection of streptozotocin and and this was followed by treatment with Valsartan. Levels of blood glucose, kidney weight and body weight, as well as proteinuria were measured. Samples of the kidneys were also histologically examined. The relative levels of Jagged1, Notch1, Notch intracellular domain 1 (NICD1), Hes family BHLH transcription factor 1 (Hes1) and Hes-related family BHLH transcription factor with YRPW motif 1 expression (Hey1) in the glomeruli were determined by immunohistochemical analysis, western blot analysis and RT-qPCR. The B-Cell CLL/Lymphoma 2 (Bcl-2) and p53 pathways were examined by western blot analysis. Apoptosis and detachment of podocytes from the glomerular basement membrane were examined using a TUNEL assay, flow cytometric analysis and ELISA. The number of podocytes was quantified by measuring Wilms tumor-1 (WT-1) staining. We noted that the expression of Jagged1, Notch1, NICD1, Hes1 and Hey1 was increased in a time-dependent manner in the glomeruli of mice with streptozotocin (STZ)-induced diabetes. Moreover, in diabetic mice, Valsartan significantly reduced kidney weight and proteinuria, and mitigated the pathogenic processes in the kidneys. Valsartan also inhibited the activation of Notch, Bcl-2 and p53 pathways and ameliorated podocyte loss in the glomeruli of mice with STZ-induced diabetes. Taken together, these findings indicated that Valsartan exerted a beneficial effect on reducing podocyte loss, which is associated with inhibition of Notch pathway activation in the glomeruli of diabetic mice.
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Copy and paste a formatted citation
Spandidos Publications style
Gao F, Yao M, Cao Y, Liu S, Liu Q and Duan H: Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway. Int J Mol Med 37: 1328-1336, 2016.
APA
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., & Duan, H. (2016). Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway. International Journal of Molecular Medicine, 37, 1328-1336. https://doi.org/10.3892/ijmm.2016.2525
MLA
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., Duan, H."Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway". International Journal of Molecular Medicine 37.5 (2016): 1328-1336.
Chicago
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., Duan, H."Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway". International Journal of Molecular Medicine 37, no. 5 (2016): 1328-1336. https://doi.org/10.3892/ijmm.2016.2525
Copy and paste a formatted citation
x
Spandidos Publications style
Gao F, Yao M, Cao Y, Liu S, Liu Q and Duan H: Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway. Int J Mol Med 37: 1328-1336, 2016.
APA
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., & Duan, H. (2016). Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway. International Journal of Molecular Medicine, 37, 1328-1336. https://doi.org/10.3892/ijmm.2016.2525
MLA
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., Duan, H."Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway". International Journal of Molecular Medicine 37.5 (2016): 1328-1336.
Chicago
Gao, F., Yao, M., Cao, Y., Liu, S., Liu, Q., Duan, H."Valsartan ameliorates podocyte loss in diabetic mice through the Notch pathway". International Journal of Molecular Medicine 37, no. 5 (2016): 1328-1336. https://doi.org/10.3892/ijmm.2016.2525
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