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Article

Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes

  • Authors:
    • Luqun Liang
    • Shuang Li
    • Huiming Liu
    • Yanwen Mao
    • Lingling Liu
    • Xiaohuan Zhang
    • Wei Peng
    • Ying Xiao
    • Fan Zhang
    • Mingjun Shi
    • Yuanyuan Wang
    • Bing Guo
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
  • Article Number: 1341
    |
    Published online on: September 22, 2021
       https://doi.org/10.3892/etm.2021.10776
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Abstract

Ski‑related novel protein N (SnoN) negatively regulates the transforming growth factor‑β1 (TGF‑β1)/Smads signaling pathway and is present at a low level during diabetic nephropathy (DN), but its underlying regulatory mechanism is currently unknown. The present study aimed to assess the effects of insulin‑controlled blood glucose on renal SnoN expression and fibrosis in rats with diabetes mellitus (DM). Streptozotocin‑induced DM rats were treated with insulin glargine (INS group) following successful model establishment. Blood samples were collected and centrifuged for biochemical indexes and the kidneys were collected for morphological analysis. In vitro, rat renal proximal tubular epithelial cells were treated with high‑glucose medium for 24 h and transferred to normal glucose medium for 24 h. The expression levels of TGF‑β1, SnoN, Smad ubiquitin regulatory factor 2 (Smurf2), Arkadia, Smads, E‑cadherin, α‑smooth muscle actin and collagen III were assessed by western blotting and immunohistochemistry. The ubiquitylation of SnoN was detected by immunoprecipitation, and the expression levels of SnoN mRNA were evaluated by reverse transcription‑quantitative PCR. The biochemical parameters and morphology indicated that renal fibrosis was notable in the DM group and mitigated in the INS group. Compared with the control group, TGF‑β1, phosphor (p)‑Smad2, p‑Smad3, Smurf2 and Arkadia levels were enhanced in the DM group, and the levels of SnoN protein were decreased, whereas the levels of SnoN mRNA and ubiquitylation were increased in renal tissues. Notably, treatment with insulin reversed this trend. Furthermore, changing the glucose levels in the medium from high to normal glucose suppressed the epithelial‑mesenchymal transition of NRK‑52E cells by restoring the SnoN protein levels, and this phenomenon was impaired by the knockout of SnoN. SnoN protein levels were likely reduced through a mechanism enhanced by the ubiquitin proteasome system, which reversed the transcriptional activation of SnoN during DN progression. In addition, controlling blood glucose may delay DN fibrosis by rescuing the protein stability of SnoN.
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Copy and paste a formatted citation
Spandidos Publications style
Liang L, Li S, Liu H, Mao Y, Liu L, Zhang X, Peng W, Xiao Y, Zhang F, Shi M, Shi M, et al: Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes. Exp Ther Med 22: 1341, 2021.
APA
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X. ... Guo, B. (2021). Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes. Experimental and Therapeutic Medicine, 22, 1341. https://doi.org/10.3892/etm.2021.10776
MLA
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X., Peng, W., Xiao, Y., Zhang, F., Shi, M., Wang, Y., Guo, B."Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes". Experimental and Therapeutic Medicine 22.5 (2021): 1341.
Chicago
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X., Peng, W., Xiao, Y., Zhang, F., Shi, M., Wang, Y., Guo, B."Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1341. https://doi.org/10.3892/etm.2021.10776
Copy and paste a formatted citation
x
Spandidos Publications style
Liang L, Li S, Liu H, Mao Y, Liu L, Zhang X, Peng W, Xiao Y, Zhang F, Shi M, Shi M, et al: Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes. Exp Ther Med 22: 1341, 2021.
APA
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X. ... Guo, B. (2021). Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes. Experimental and Therapeutic Medicine, 22, 1341. https://doi.org/10.3892/etm.2021.10776
MLA
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X., Peng, W., Xiao, Y., Zhang, F., Shi, M., Wang, Y., Guo, B."Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes". Experimental and Therapeutic Medicine 22.5 (2021): 1341.
Chicago
Liang, L., Li, S., Liu, H., Mao, Y., Liu, L., Zhang, X., Peng, W., Xiao, Y., Zhang, F., Shi, M., Wang, Y., Guo, B."Blood glucose control contributes to protein stability of Ski‑related novel protein N in a rat model of diabetes". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1341. https://doi.org/10.3892/etm.2021.10776
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