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Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells

  • Authors:
    • Xiao Chen
    • Yang Yang
    • Chenxu Liu
    • Zhigao Chen
    • Dongdong Wang

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  • Published online on: November 26, 2018     https://doi.org/10.3892/ijmm.2018.3999
  • Pages: 709-716

  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Astragaloside IV (AST) is the major active saponin in Astragalus membranaceus and, reportedly, has a variety of pharmacological activities. However, the potential of AST to ameliorate high glucose‑mediated renal tubular epithelial‑mesenchymal transition (EMT) remains undetermined. The aim of the present research was to explore the effect and mechanism of AST in EMT of renal tubular epithelial cells, as an underlying mechanism of renal fibrosis and a vital feature involved in diabetic nephropathy. The effect of AST on the EMT of renal tubular epithelial cells (HK‑2) stimulated by high glucose was investigated and it was attempted to elucidate the potential underlying mechanism. The expression of E‑cadherin and α‑smooth muscle actin were determined by western blotting and immunofluorescence assays. The expression of the mammalian target of rapamycin complex 1 (mTORC1)/ ribosomal protein S6 kinase β‑1 (p70S6K) signaling pathway and protein levels of four transcriptional factors (snail, slug, twist and zinc finger E‑box‑binding homeobox 1) were also determined by western blotting. Additionally, extracellular matrix components, including fibronectin (FN) and collagen type IV (Col IV) were detected by ELISA. The results suggested that the EMT of HK‑2 cells and the mTORC1/p70S6K pathway were activated by high glucose. The expression of snail and twist in HK‑2 cells was elevated by high glucose. Furthermore, extracellular matrix components, FN and Col IV, were increased in HK‑2 cells cultured with high glucose. In turn, treatment with AST reduced EMT features in HK‑2 cells, inhibited mTORC1/p70S6K pathway activation, downregulated expression of snail and twist, and reduced secretion of FN and Col IV. In summary, the findings suggested that AST ameliorates high glucose‑mediated renal tubular EMT by blocking the mTORC1/p70S6K signaling pathway in HK‑2 cells.
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February-2019
Volume 43 Issue 2

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

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  • Impact Factor: 5.7
  • Ranked Medicine Research and Experimental
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  • CiteScore: 12.3
  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
Chen X, Yang Y, Liu C, Chen Z and Wang D: Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells. Int J Mol Med 43: 709-716, 2019.
APA
Chen, X., Yang, Y., Liu, C., Chen, Z., & Wang, D. (2019). Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells. International Journal of Molecular Medicine, 43, 709-716. https://doi.org/10.3892/ijmm.2018.3999
MLA
Chen, X., Yang, Y., Liu, C., Chen, Z., Wang, D."Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells". International Journal of Molecular Medicine 43.2 (2019): 709-716.
Chicago
Chen, X., Yang, Y., Liu, C., Chen, Z., Wang, D."Astragaloside IV ameliorates high glucose‑induced renal tubular epithelial‑mesenchymal transition by blocking mTORC1/p70S6K signaling in HK‑2 cells". International Journal of Molecular Medicine 43, no. 2 (2019): 709-716. https://doi.org/10.3892/ijmm.2018.3999