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Novel bioactivity of NHERF1 in corneal neovascularization

  • Basic Science
  • Published:
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Abstract

Purpose

This paper aimed to determine the involvement of Na+/H+ exchanger regulatory factor 1 (NHERF1) in experimental murine corneal neovascularization (NV), and to study the effect of NHERF1 on the biological properties of HUVEC and related mechanisms.

Methods

Using loss- and gain-function, we investigated the biological effects of NHERF1 on HUVEC. Western blotting was used to detect the expression of NHERF1 in cells. A carboxyfluorescein succinimidyl ester (CFSE) labeling assay and scarification test were used to measure the proliferation and migration activity, respectively, of HUVEC. The cell cycle distribution of the cells was assessed by flow cytometry analysis. The effect of NHERF1 on the phosphorylation levels of Akt and the changes of matrix metalloproteinase (MMP)-2 and MMP-9 levels were detected by western blotting analysis. Change in the NHERF1 expression in the alkali burn-induced corneal NV model was detected by microarray, real-time PCR, and immunofluorescence.

Results

Overexpression of exogenous NHERF1 in HUVEC slightly inhibited the proliferation and significantly reduced the migration of the cells. NHERF1 also significantly downregulated Akt1 phosphorylation induced by platelet-derived growth factor BB (PDGF-BB) and the secretion of MMP-2 and MMP-9 compared with control cells. NHERF1 was upregulated in corneas challenged with alkali burns.

Conclusions

Our results indicated that NHERF1 might serve as a potential target for manipulating neovascularization-related diseases. This discovery contributes to a better understanding of the bioactivity of NHERF1 in angiogenesis.

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Acknowledgments

The work was supported by the State Key Basic Research Project (2007CB516705) and Shandong Sci-Tec Foundation (2006GG1102020). Yiqiang Wang is partially supported by the Taishan Scholar Program (QDU-EYE) of China.

Financial support

There is no financial relationship with the organization that sponsored the research. The authors have full control of all primary data and we agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data upon request.

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Authors and Affiliations

  1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China

    Peng Chen, Ye Wang, Lingling Yang, Changyou Li, Yao Wang, Lixin Xie & Yiqiang Wang

  2. Shandong Eye Institute, #5 Yan’erdao Road, Qingdao, 266071, China

    Yiqiang Wang

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  1. Peng Chen
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  2. Ye Wang
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Correspondence to Yiqiang Wang.

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Chen, P., Wang, Y., Yang, L. et al. Novel bioactivity of NHERF1 in corneal neovascularization. Graefes Arch Clin Exp Ophthalmol 250, 1615–1625 (2012). https://doi.org/10.1007/s00417-012-2094-5

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  • DOI: https://doi.org/10.1007/s00417-012-2094-5

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