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Article

AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway

  • Authors:
    • Yuhong Ma
    • Weizu Li
    • Yanyan Yin
    • Weiping Li
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, College of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China
  • Pages: 1667-1674
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    Published online on: April 17, 2015
       https://doi.org/10.3892/ijmm.2015.2188
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Abstract

Endothelial cell apoptosis plays an important role in the pathophysiological mechanisms of vascular complications in diabetes mellitus (DM). NADPH oxidase 4 (Nox4)-dependent reactive oxygen species (ROS) aggregation is the main cause of vascular endothelial cell apoptosis. The transforming growth factor-β1 (TGF-β1)/Smad2 signaling pathway is involved in the apoptosis of several types of cells. However, the association between vascular endothelial cell apoptosis and Nox4, and the involvement of the TGF-β1/Smad2 signaling pathway in vascular endothelial cell apoptosis remain unclear. In the present study, we aimed to investigate the role of Nox4-dependent ROS production and to determine the involvement of the TGF-β1/Smad2 signaling pathway in endothelial cell apoptosis induced by oxidative stress which causes vascular injury in DM. We demonstrated that hydrogen peroxide (H2O2) increased Nox4-dependent-ROS aggregation, as well as the expression of TGF-β1, Smad2, Bax and caspase-3, decreased Bcl-2 expression and increased the apoptosis of human umbilical vein endothelial cells (HUVECs). Treatment with diphenyliodonium (DPI), a specific inhibitor of Nox4 or astragaloside Ⅳ (AST Ⅳ), a monomer located in an extract of astragaloside, decreased Nox4 expression and the levels of ROS, decreased TGF-β1 and Smad2 expression, altered the expression of apoptosis-related genes and decreased the apoptosis of HUVECs. Treatment with LY2109761, a selective inhibitor of the TGF-β1/Smad2 pathway, produced results similar to those of DPI; however, LY2109761 had no effect on Nox4 expression and ROS levels. Taken together, the findings of the present study suggest that H2O2 contributes to HUVEC apoptosis by inducing Nox4-dependent ROS aggregation and activating the TGF-β1/Smad2 signaling pathway. Our data indicate that the protective effects of AST Ⅳ against vascular endothelial cell apoptosis in DM are mainly associated with the decrease in Nox4 expression through the TGF-β1/Smad2 signaling pathway. Furthermore, the inhibition of the activation of the TGF-β1/Smad2 signaling pathway may be another potential therapeutic strategy in the treatment of DM.
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Copy and paste a formatted citation
Spandidos Publications style
Ma Y, Li W, Yin Y and Li W: AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway. Int J Mol Med 35: 1667-1674, 2015.
APA
Ma, Y., Li, W., Yin, Y., & Li, W. (2015). AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway. International Journal of Molecular Medicine, 35, 1667-1674. https://doi.org/10.3892/ijmm.2015.2188
MLA
Ma, Y., Li, W., Yin, Y., Li, W."AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway". International Journal of Molecular Medicine 35.6 (2015): 1667-1674.
Chicago
Ma, Y., Li, W., Yin, Y., Li, W."AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway". International Journal of Molecular Medicine 35, no. 6 (2015): 1667-1674. https://doi.org/10.3892/ijmm.2015.2188
Copy and paste a formatted citation
x
Spandidos Publications style
Ma Y, Li W, Yin Y and Li W: AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway. Int J Mol Med 35: 1667-1674, 2015.
APA
Ma, Y., Li, W., Yin, Y., & Li, W. (2015). AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway. International Journal of Molecular Medicine, 35, 1667-1674. https://doi.org/10.3892/ijmm.2015.2188
MLA
Ma, Y., Li, W., Yin, Y., Li, W."AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway". International Journal of Molecular Medicine 35.6 (2015): 1667-1674.
Chicago
Ma, Y., Li, W., Yin, Y., Li, W."AST Ⅳ inhibits H2O2-induced human umbilical vein endothelial cell apoptosis by suppressing Nox4 expression through the TGF-β1/Smad2 pathway". International Journal of Molecular Medicine 35, no. 6 (2015): 1667-1674. https://doi.org/10.3892/ijmm.2015.2188
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