Discovery of Ezrin Expression as a Potential Biomarker for Chemically Induced Ocular Irritation Using Human Corneal Epithelium Cell Line and a Reconstructed Human Cornea-like Epithelium Model

Dong Jin Ye, Yeo Jung Kwon, Hyoung Seok Baek, Sangyun Shin, Choongho Lee, Jun Won Yun, KiTaek Nam, Kyung Min Lim, Young Jin Chun

Research output: Contribution to journalArticle

Abstract

Numerous studies have attempted to develop a new in vitro eye irritation test (EIT). To obtain more reliable results from EIT, potential new biomarkers that reflect eye irritation by chemicals must be identified. We investigated candidate biomarkers for eye irritation, using a proteomics approach. Sodium lauryl sulfate (SLS) or benzalkonium chloride (BAC) was applied on a reconstructed human cornea-like epithelium model, MCTT HCE, and corneal protein expression was examined by two-dimensional gel electrophoresis. We found that ezrin (EZR) was significantly upregulated by SLS or BAC. In addition, upregulation of EZR in immortalized human corneal cells treated with SLS or BAC was confirmed by quantitative reverse transcription-PCR and western blot analysis. Furthermore, other well-known eye irritants such as cetylpyridinium bromide, Triton X-100, cyclohexanol, ethanol, 2-methyl-1-pentanol, and sodium hydroxide significantly increased EZR expression in immortalized human corneal cells. Induction of EZR promoter activity in irritant-treated human corneal cells was confirmed by a luciferase gene reporter assay. In conclusion, EZR expression may be a potential biomarker for detecting eye irritation, which may substantially improve the performance of in vitro EIT.

Original languageEnglish
Pages (from-to)335-346
Number of pages12
JournalToxicological Sciences
Volume165
Issue number2
DOIs
Publication statusPublished - 2018 Oct 1

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Corneal Epithelium
Biomarkers
Cornea
Benzalkonium Compounds
Epithelium
Cells
Cell Line
Sodium Dodecyl Sulfate
Irritants
Cyclohexanols
Cetylpyridinium
Sodium Hydroxide
Octoxynol
Transcription
Electrophoresis
Luciferases
Bromides
Assays
Ethanol
Electrophoresis, Gel, Two-Dimensional

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Ye, Dong Jin ; Kwon, Yeo Jung ; Baek, Hyoung Seok ; Shin, Sangyun ; Lee, Choongho ; Yun, Jun Won ; Nam, KiTaek ; Lim, Kyung Min ; Chun, Young Jin. / Discovery of Ezrin Expression as a Potential Biomarker for Chemically Induced Ocular Irritation Using Human Corneal Epithelium Cell Line and a Reconstructed Human Cornea-like Epithelium Model. In: Toxicological Sciences. 2018 ; Vol. 165, No. 2. pp. 335-346.
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abstract = "Numerous studies have attempted to develop a new in vitro eye irritation test (EIT). To obtain more reliable results from EIT, potential new biomarkers that reflect eye irritation by chemicals must be identified. We investigated candidate biomarkers for eye irritation, using a proteomics approach. Sodium lauryl sulfate (SLS) or benzalkonium chloride (BAC) was applied on a reconstructed human cornea-like epithelium model, MCTT HCE, and corneal protein expression was examined by two-dimensional gel electrophoresis. We found that ezrin (EZR) was significantly upregulated by SLS or BAC. In addition, upregulation of EZR in immortalized human corneal cells treated with SLS or BAC was confirmed by quantitative reverse transcription-PCR and western blot analysis. Furthermore, other well-known eye irritants such as cetylpyridinium bromide, Triton X-100, cyclohexanol, ethanol, 2-methyl-1-pentanol, and sodium hydroxide significantly increased EZR expression in immortalized human corneal cells. Induction of EZR promoter activity in irritant-treated human corneal cells was confirmed by a luciferase gene reporter assay. In conclusion, EZR expression may be a potential biomarker for detecting eye irritation, which may substantially improve the performance of in vitro EIT.",
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Discovery of Ezrin Expression as a Potential Biomarker for Chemically Induced Ocular Irritation Using Human Corneal Epithelium Cell Line and a Reconstructed Human Cornea-like Epithelium Model. / Ye, Dong Jin; Kwon, Yeo Jung; Baek, Hyoung Seok; Shin, Sangyun; Lee, Choongho; Yun, Jun Won; Nam, KiTaek; Lim, Kyung Min; Chun, Young Jin.

In: Toxicological Sciences, Vol. 165, No. 2, 01.10.2018, p. 335-346.

Research output: Contribution to journalArticle

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