May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Protection of Human Corneal Epithelial Cells From Hypoxia-Induced Disruption of Barrier Function by Keratinocyte Growth Factor
Author Affiliations & Notes
  • S. Teranishi
    Yamaguchi University School of Medicine, Ube City, Japan
    Department of Ophthalmology,
  • K. Kimura
    Yamaguchi University School of Medicine, Ube City, Japan
    Department of Ocular Pathophysiology,
  • K. Kawamoto
    Yamaguchi University School of Medicine, Ube City, Japan
    Department of Ophthalmology,
  • T. Nishida
    Yamaguchi University School of Medicine, Ube City, Japan
    Department of Ophthalmology,
  • Footnotes
    Commercial Relationships  S. Teranishi, None; K. Kimura, None; K. Kawamoto, None; T. Nishida, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2550. doi:https://doi.org/
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      S. Teranishi, K. Kimura, K. Kawamoto, T. Nishida; Protection of Human Corneal Epithelial Cells From Hypoxia-Induced Disruption of Barrier Function by Keratinocyte Growth Factor. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2550. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The possible detrimental effect of hypoxia on the barrier function of corneal epithelial cells and whether keratinocyte growth factor (KGF) might protect against such an effect were investigated.

Methods: : Simian virus 40-transformed human corneal epithelial (HCE) cells were cultured for 4 days to allow establishment of barrier function. They were then deprived of serum for 24 hours before exposure to 1% (hypoxia) or 21% (normoxia) oxygen for 24 hours. Barrier function was evaluated by measurement of transepithelial electrical resistance (TER). The localization of the tight junctional proteins ZO-1 and occludin was determined by immunofluorescence microscopy, and the expression of these proteins as well as the phosphorylation of the mitogen-activated protein kinases ERK, p38, and JNK were examined by immunoblot analysis.

Results: : Hypoxia induced a decrease in the TER of HCE cells compared with that of those maintained under normoxia. The localization of ZO-1 at cell-cell borders was disrupted by hypoxia, whereas the distribution of occludin was not affected. Hypoxia also induced down-regulation of ZO-1 as well as a decrease in the phosphorylation of ERK, without affecting the phosphorylation of p38 or JNK. All these effects of hypoxia were inhibited by KGF. The effects of KGF on TER and ZO-1 localization in cells exposed to hypoxia were inhibited by PD98059, an inhibitor of ERK signaling. Neither hypoxia nor KGF exhibited mitogenic or cytotoxic effects in HCE cells.

Conclusions: : Hypoxia induces disruption of the barrier function of human corneal epithelial cells by eliciting the redistribution and degradation of ZO-1, and this effect is inhibited by KGF in a manner dependent on ERK activation.

Keywords: cornea: epithelium • hypoxia • growth factors/growth factor receptors 
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