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
- 주제(키워드) ezrin , 3D human corneal epithelial model , immortalized corneal cell , eye irritation , proteomic analysis
- 주제(기타) Toxicology
- 설명문(일반) [Ye, Dong-Jin; Kwon, Yeo-Jung; Baek, Hyoung-Seok; Shin, Sangyun; Chun, Young-Jin] Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea; [Lee, Choongho] Dongguk Univ, Coll Pharm, Goyang 10326, South Korea; [Yun, Jun-Won] Catholic Univ Korea, Dept Biotechnol, Bucheon 14662, South Korea; [Nam, Ki Taek] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Brain Korea PLUS Project Med Sci 21, Seoul 03722, South Korea; [Lim, Kyung-Min] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 OXFORD UNIV PRESS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156634
- 본문언어 영어
- Published As http://dx.doi.org/10.1093/toxsci/kfy134
초록/요약
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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