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Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells

  • Authors:
    • Lin Zhao
    • Jianming Wang
    • Yi Zhang
    • Lijun Wang
    • Miao Yu
    • Feng Wang
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 436-444
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    Published online on: April 30, 2020
       https://doi.org/10.3892/mmr.2020.11103
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Abstract

Posterior capsular opacification (PCO) is the main complication following cataract surgery. The proliferation of the residual lens epithelial cells (LECs) serves an important role in PCO formation. The authors' previous study revealed that vitamin C inhibited the proliferation of human LECs by increasing the rapid degradation of hypoxia‑inducible factor‑1 (HIF‑1α), and hence inhibited the expression of vascular endothelial growth factor (VEGF). The present study aimed to further investigate the mechanisms underlying the effects of vitamin C on the expression levels of VEGF. The present study demonstrated that the HIF‑1 inhibitor BAY 87‑2243 significantly inhibited the cell proliferation and the expression levels of VEGF in LECs through the use of colony formation, western blotting and ELISA assays. Moreover, it was revealed that vitamin C could further inhibit the cell proliferation and the expression levels of VEGF in LECs following the cotreatment with the HIF‑1 inhibitor. The proline hydroxylation of HIF‑1α by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF‑1α. Thus, the present study subsequently used three PHD inhibitors to investigate their effects on the expression levels of VEGF; it was found that the PHD2 specific inhibitor increased the expression levels of VEGF to the greatest extent. Moreover, the genetic knockdown of PHD2 by lentiviral transfection also significantly increased the expression levels of VEGF, whereas the PHD2 specific inhibitor did not alter the expression levels of VEGF in the PHD2 knockdown LECs. AKT kinase activity is an important mediator known to upregulate VEGF expression. Using an immunoprecipitation assay to isolate endogenous AKT, it was demonstrated that AKT was prolyl hydroxylated by PHD2, which inhibited its activity. It was also revealed that vitamin C enhanced the proline‑hydroxylation and inhibited the activity of AKT. Furthermore, an AKT inhibitor increased the effects of vitamin C on the expression levels of VEGF. However, the AKT inhibitor did not affect the expression levels of glucose transporter 1, which is a HIF‑1α target gene. In conclusion, the findings of the present study suggested that vitamin C may inhibit the expression levels of VEGF via HIF‑1α‑dependent and AKT‑dependent pathways in LECs.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao L, Wang J, Zhang Y, Wang L, Yu M and Wang F: Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells. Mol Med Rep 22: 436-444, 2020.
APA
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., & Wang, F. (2020). Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells. Molecular Medicine Reports, 22, 436-444. https://doi.org/10.3892/mmr.2020.11103
MLA
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., Wang, F."Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells". Molecular Medicine Reports 22.1 (2020): 436-444.
Chicago
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., Wang, F."Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells". Molecular Medicine Reports 22, no. 1 (2020): 436-444. https://doi.org/10.3892/mmr.2020.11103
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao L, Wang J, Zhang Y, Wang L, Yu M and Wang F: Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells. Mol Med Rep 22: 436-444, 2020.
APA
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., & Wang, F. (2020). Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells. Molecular Medicine Reports, 22, 436-444. https://doi.org/10.3892/mmr.2020.11103
MLA
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., Wang, F."Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells". Molecular Medicine Reports 22.1 (2020): 436-444.
Chicago
Zhao, L., Wang, J., Zhang, Y., Wang, L., Yu, M., Wang, F."Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells". Molecular Medicine Reports 22, no. 1 (2020): 436-444. https://doi.org/10.3892/mmr.2020.11103
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