GSK-3β inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes

  • Authors:
    • Jia Wan
    • Peng Li
    • Dong‑Wei Liu
    • Ying Chen
    • Hai‑Zhen Mo
    • Ben‑Guo Liu
    • Wen‑Jie Chen
    • Xiao‑Qing Lu
    • Jia Guo
    • Qian Zhang
    • Ying‑Jin Qiao
    • Zhang‑Suo Liu
    • Guang‑Rui Wan
  • View Affiliations

  • Published online on: June 23, 2016     https://doi.org/10.3892/mmr.2016.5441
  • Pages: 1771-1784
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Abstract

The mechanism underlying epithelial‑to‑mesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase 3β (GSK‑3β) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)‑6‑bromoindirubin‑3'‑oxime (BIO), an inhibitor of GSK‑3β, on EMT and glomerular injury. The resulting data showed that the activity of GSK‑3β was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including α‑smooth muscle actin (α‑SMA) and fibronectin. The expression levels of β‑catenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitamin D receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HG‑mediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK‑3β may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN.
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August-2016
Volume 14 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wan J, Li P, Liu DW, Chen Y, Mo HZ, Liu BG, Chen WJ, Lu XQ, Guo J, Zhang Q, Zhang Q, et al: GSK-3β inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes. Mol Med Rep 14: 1771-1784, 2016
APA
Wan, J., Li, P., Liu, D., Chen, Y., Mo, H., Liu, B. ... Wan, G. (2016). GSK-3β inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes. Molecular Medicine Reports, 14, 1771-1784. https://doi.org/10.3892/mmr.2016.5441
MLA
Wan, J., Li, P., Liu, D., Chen, Y., Mo, H., Liu, B., Chen, W., Lu, X., Guo, J., Zhang, Q., Qiao, Y., Liu, Z., Wan, G."GSK-3β inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes". Molecular Medicine Reports 14.2 (2016): 1771-1784.
Chicago
Wan, J., Li, P., Liu, D., Chen, Y., Mo, H., Liu, B., Chen, W., Lu, X., Guo, J., Zhang, Q., Qiao, Y., Liu, Z., Wan, G."GSK-3β inhibitor attenuates urinary albumin excretion in type 2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes". Molecular Medicine Reports 14, no. 2 (2016): 1771-1784. https://doi.org/10.3892/mmr.2016.5441