Open Access

Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway

  • Authors:
    • Jiaqiong Lin
    • Xiaoyong Li
    • Yan Lin
    • Zena Huang
    • Wen Wu
  • View Affiliations

  • Published online on: November 19, 2020     https://doi.org/10.3892/mmr.2020.11706
  • Article Number: 67
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In recent years hydrogen sulfide (H2S) has demonstrated vasculoprotective effects against cell death, which suggests its promising therapeutic potential for numerous types of disease. Additionally, a protective effect of exogenous H2S in HG‑induced injuries in HUVECs was demonstrated, suggesting a potential protective effect for diabetic vascular complications. The present study aimed to investigate the mechanism accounting for the cytoprotective role of exogenous H2S against high glucose [HG (40 mM glucose)]‑induced injury and inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to HG for 24 h to establish an in vitro model of HG‑induced cytotoxicity. The cells were pretreated with sodium hydrosulfide (NaHS), a donor of H2S, or inhibitors of necroptosis and p38 MAPK prior to the exposure to HG. Cell viability, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), IL‑1β, IL‑6, IL‑8, TNF‑α, phosphorylated‑(p)38 and receptor‑interacting protein 3 (RIP3) expression levels were detected using the indicated methods, including Cell Counting Kit 8, fluorescence detection, western blotting, immunofluorescence assay and ELISAs. The results demonstrated that necroptosis and the p38 MAPK signaling pathway mediated HG‑induced injury and inflammation. Notably, NaHS was discovered to significantly ameliorate p38 MAPK/necroptosis‑mediated injury and inflammation in response to HG, as evidenced by an increase in cell viability, a decrease in ROS generation and loss of MMP, as well as the reduction in the secretion of proinflammatory cytokines. In addition, the upregulated expression of RIP3 induced by HG was repressed by treatment with SB203580, while the HG‑induced upregulation of p‑p38 expression levels were significantly downregulated following the treatment of Nec‑1 and RIP3‑siRNA. In conclusion, the findings of the present study indicated that NaHS may protect HUVECs against HG‑induced injury and inflammation by inhibiting necroptosis via the p38 MAPK signaling pathway, which may represent a promising drug for the therapy of diabetic vascular complications.
View Figures
View References

Related Articles

Journal Cover

January-2021
Volume 23 Issue 1

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Lin J, Li X, Lin Y, Huang Z and Wu W: Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway. Mol Med Rep 23: 67, 2021
APA
Lin, J., Li, X., Lin, Y., Huang, Z., & Wu, W. (2021). Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway. Molecular Medicine Reports, 23, 67. https://doi.org/10.3892/mmr.2020.11706
MLA
Lin, J., Li, X., Lin, Y., Huang, Z., Wu, W."Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway". Molecular Medicine Reports 23.1 (2021): 67.
Chicago
Lin, J., Li, X., Lin, Y., Huang, Z., Wu, W."Exogenous sodium hydrosulfide protects against high glucose‑induced injury and inflammation in human umbilical vein endothelial cells by inhibiting necroptosis via the p38 MAPK signaling pathway". Molecular Medicine Reports 23, no. 1 (2021): 67. https://doi.org/10.3892/mmr.2020.11706