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Egr1 gene expression as a potential biomarker for in vitro prediction of ocular toxicity

Title
Egr1 gene expression as a potential biomarker for in vitro prediction of ocular toxicity
Authors
Hwang D.-B.Kim S.-Y.Won D.-H.Kim C.Shin Y.-S.Park J.-H.Chun Y.-J.Lim K.-M.Yun J.-W.
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2021
Journal Title
Pharmaceutics
ISSN
1999-4923JCR Link
Citation
Pharmaceutics vol. 13, no. 10
Keywords
BiomarkerEarly growth response-1Eye irritationImmortalized corneal cellReporter vector system
Publisher
MDPI
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
Animal models are used for preclinical toxicity studies, and the need for in vitro alternative methods has been strongly raised. Our study aims to elucidate the potential mechanism of change in EGR1 expression under situations of toxic injury and to develop an Egr1 promoter–luciferase gene reporter assay for an in vitro alternative method for toxicity prediction in drug discovery. We first found an increase in early growth response-1 (EGR1) mRNA/protein expressions in the liver and kidney of cisplatin-treated injured rats. Additionally, the EGR1 protein level was also elevated under situations of ocular injury after sodium lauryl sulfate (SLS) eye drops. These in vivo observations on injury-related EGR1 induction were confirmed by in vitro studies, where human corneal epithelial cells were treated with representative irritants (SLS and benzalkonium chloride) and 17 chemicals having different UN GHS irritant categories. Additionally, our results suggest the involvement of ERK, JNK, p38 MAPK pathways in EGR1 elevation in response to gamma-butyrolactone-induced injury. As EGR1 is considered to be a pivotal factor in proliferation and regeneration, siRNA-mediated knockdown of Egr1 promoted cytotoxic potential through a delay of injury-related recovery. More importantly, the elevation of promoter activities was observed by various irritants in cells transfected with Egr1 promoter-reporter vector. In conclusion, Egr1 can be a potential biomarker in a promoter-reporter system to improve the accuracy of in vitro predictions for ocular irritation. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
DOI
10.3390/pharmaceutics13101584
Appears in Collections:
약학대학 > 약학과 > Journal papers
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