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Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia

  • Authors:
    • Jianfeng Zhao
    • Yu Geng
    • Hairong Hua
    • Biyun Cun
    • Qianbo Chen
    • Xiaoting Xi
    • Liushu Yang
    • Yan Li
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650031, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1404-1412
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    Published online on: August 21, 2015
       https://doi.org/10.3892/etm.2015.2697
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Abstract

The aim of the present study was to examine the mechanisms through which fenofibrate inhibits the ability of human retinal pigment epithelial cells (RPE cells) exposed to hypoxia to stimulate the proliferation and migration of human umbilical vein endothelial cells (HUVECs). For this purpose, RPE cells and HUVECs were divided into the following groups: RPE-normoxia, RPE + fenofibrate, RPE-hypoxia, RPE hypoxia + fenofibrate; HUVECs normal culture and HUVECs + RPE-hypoxia culture supernatant. RPE cell hypoxia was induced by cobalt(II) chloride (CoCl2). A superoxide anion probe was used to measure the production of superoxide anion, which is indicative of hypoxic conditions. Cell proliferation was assessed by MTT assay, and the expression of vascular endothelial growth factor C (VEGFC) and vascular endothelial growth factor receptor-3 (VEGFR-3) in the RPE cell culture supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The migration ability of the HUVECs was determined by scratch-wound assay, and the angiogenic ability of the HUVECs was examined by measuring cell lumen formation. The mRNA and protein expression levels of VEGFC and VEGFR-3 in the RPE cells were measured by RT-qPCR and western blot analysis, respectively. Our results revealed that fenofibrate inhibited the increase in the expression and release of VEGFC and VEGFR-3 into the RPE cell culture supernatant induced by exposure to hypoxia. The culture of HUVECs in medium supernatant of RPE cells epxosed to hypoxia enhanced the viability and migration ability of the HUVECs and promoted lumen formation; these effects were inhibited by fenofibrate. In conclusion, our data demonstrated that the exposure of RPE cells to hypoxia induced the expression and release of VEGFC and VEGFR-3 into the cell culture supernatant. The culture of HUVECs in conditioned medium from RPE cells exposed to hypoxia increased VEGFC and VEGFR-3 expression, and promoted the proliferation and migration of the HUVECs, as well as capillary tube formation, suggesting that RPE cells play an important role in the formation of choroidal neovascularization resulting from hypoxia. Fenofibrate inhibited the upregulation of VEGFC and VEGFR-3 in the RPE cells exposed to hypoxia, and thus reduced the ability of HUVECs to form new blood vessels.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao J, Geng Y, Hua H, Cun B, Chen Q, Xi X, Yang L and Li Y: Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia. Exp Ther Med 10: 1404-1412, 2015.
APA
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X. ... Li, Y. (2015). Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia. Experimental and Therapeutic Medicine, 10, 1404-1412. https://doi.org/10.3892/etm.2015.2697
MLA
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X., Yang, L., Li, Y."Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia". Experimental and Therapeutic Medicine 10.4 (2015): 1404-1412.
Chicago
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X., Yang, L., Li, Y."Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia". Experimental and Therapeutic Medicine 10, no. 4 (2015): 1404-1412. https://doi.org/10.3892/etm.2015.2697
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao J, Geng Y, Hua H, Cun B, Chen Q, Xi X, Yang L and Li Y: Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia. Exp Ther Med 10: 1404-1412, 2015.
APA
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X. ... Li, Y. (2015). Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia. Experimental and Therapeutic Medicine, 10, 1404-1412. https://doi.org/10.3892/etm.2015.2697
MLA
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X., Yang, L., Li, Y."Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia". Experimental and Therapeutic Medicine 10.4 (2015): 1404-1412.
Chicago
Zhao, J., Geng, Y., Hua, H., Cun, B., Chen, Q., Xi, X., Yang, L., Li, Y."Fenofibrate inhibits the expression of VEGFC and VEGFR-3 in retinal pigmental epithelial cells exposed to hypoxia". Experimental and Therapeutic Medicine 10, no. 4 (2015): 1404-1412. https://doi.org/10.3892/etm.2015.2697
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