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VEGF differentially regulates transcription and translation of ZO-1α+ and ZO-1α− and mediates trans-epithelial resistance in cultured endothelial and epithelial cells

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Abstract

Tight junctions (TJ) between retinal pigmented epithelial (RPE) and retinal endothelial cells maintain the outer and inner blood-retinal barrier, and the breakdown of these barriers is associated with retinal diseases. Vascular endothelial growth factor (VEGF) increases vascular permeability and is thought to be involved in age-related maculopathy. However, to date, little is known about the effect of VEGF on RPE cell junctions. We have investigated the effect of VEGF on TJ formation by examining two essential proteins, ZO-1α+ and ZO-1α−. Cultured vascular endothelial cells in the presence of 5 ng/ml VEGF significantly down-regulate ZO-1α+ and ZO-1α− transcripts and proteins with significant loss of their trans-epithelial resistance (TER). Immunoconfocal analysis with an anti-ZO-1 antibody has confirmed the relocation of ZO-1 protein from membrane to cytoplasm. By contrast, in the presence of 5 ng/ml VEGF, cultured RPE cells (ARPE19 and RPE51) significantly up-regulate ZO-1α+ and ZO-1α− transcripts and proteins resulting in a significant increase in their TER. Subsequent immunoconfocal analysis has demonstrated increased ZO-1 membrane assembly in VEGF-treated RPE cells. Thus, VEGF has a dual capability with respect to the regulation of the expression of some TJ proteins at the transcriptional and post-translational levels depending on cell type.

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Acknowledgements

We thank Dr. R. Marano for his valuable advice regarding the use of statistical programs.

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Authors and Affiliations

  1. Department of Molecular Ophthalmology, Lions Eye Institute, 2 Verdun Street, Nedlands, Western Australia, 6009, Australia

    Reza Ghassemifar

  2. Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia

    Reza Ghassemifar, Chooi-May Lai & P. Elizabeth Rakoczy

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  1. Reza Ghassemifar
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  2. Chooi-May Lai
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  3. P. Elizabeth Rakoczy
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Correspondence to Reza Ghassemifar.

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The authors gratefully acknowledge the Lions Eye Institute and Lions Save-Sight Foundation for financing the fellowship of R.G.

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Ghassemifar, R., Lai, CM. & Rakoczy, P.E. VEGF differentially regulates transcription and translation of ZO-1α+ and ZO-1α− and mediates trans-epithelial resistance in cultured endothelial and epithelial cells. Cell Tissue Res 323, 117–125 (2006). https://doi.org/10.1007/s00441-005-0046-7

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  • DOI: https://doi.org/10.1007/s00441-005-0046-7

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