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The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling

  • Authors:
    • Xiuji Li
    • Zongli Diao
    • Jiaxiang Ding
    • Ruixia Liu
    • Liyan Wang
    • Wen Huang
    • Wenhu Liu

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  • Published online on: December 31, 2015     https://doi.org/10.3892/ijmm.2015.2448
  • Pages: 415-422
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Transforming growth factor (TGF)-β1 is a profibrotic cytokine that plays a critical role in the progression of diabetic nephropathy (DN). Previous studies have demonstrated that the Smad transcriptional co-repressor, Ski-related novel protein N (SnoN), an antagonizer of TGF-β1/Smad signaling, is downregulated in the kidneys of diabetic rats; however, the underlying molecular mechanisms remain elusive. In the present study, we demonstrated that the upregulation of Smad ubiquitination regulatory factor-2 (Smurf2), through TGF-β1/Smad signaling, contributes to the downregulation of SnoN under high-glucose conditions in primary human renal proximal tubule epithelial cells (hRPTECs). The hRPTECs were cultured in high-glucose (30 mmol/l D-glucose) medium in the presence or absence of either the proteasome inhibitor, MG132, or the TGF-β type I receptor kinase inhibitor, SB-431542. Small interfering RNA (siRNA) was used to silence Smurf2. The expression levels of SnoN, Smurf2, Smad2 and phosphorylated (p-)Smad2 were measured by western blot analysis and RT-qPCR. The protein levels of SnoN were markedly downregulated, while its mRNA levels were increased in the hRPTECs cultured under high-glucose conditions. The protein and mRNA levels of Smurf2 were significantly increased under high-glucose conditions. The knockdown of Smurf2 increased SnoN expression in the hRPTECs cultured in high-glucose medium. Moreover, MG132 partially inhibited SnoN degradation in the hRPTECs under high-glucose conditions and SB-431542 decreased the phosphorylation of Smad2 and the expression of Smurf2 induced under high-glucose conditions. Taken together, the findings of this study demonstrate that the downregulation of SnoN expression in hRPTECs under high-glucose conditions is mediated by the increased expression of Smurf2 through the TGF-β1/Smad signaling pathway.
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February-2016
Volume 37 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Impact Factor: 5.4
  • Ranked Medicine Research and Experimental
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  • CiteScore: 10.7
  • CiteScore Rank: Q1: #35/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.994
  • SCImago Journal Rank (SJR): 0.922
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Spandidos Publications style
Li X, Diao Z, Ding J, Liu R, Wang L, Huang W and Liu W: The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling. Int J Mol Med 37: 415-422, 2016
APA
Li, X., Diao, Z., Ding, J., Liu, R., Wang, L., Huang, W., & Liu, W. (2016). The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling. International Journal of Molecular Medicine, 37, 415-422. https://doi.org/10.3892/ijmm.2015.2448
MLA
Li, X., Diao, Z., Ding, J., Liu, R., Wang, L., Huang, W., Liu, W."The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling". International Journal of Molecular Medicine 37.2 (2016): 415-422.
Chicago
Li, X., Diao, Z., Ding, J., Liu, R., Wang, L., Huang, W., Liu, W."The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling". International Journal of Molecular Medicine 37, no. 2 (2016): 415-422. https://doi.org/10.3892/ijmm.2015.2448