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Pharmaceutics
Volume 13
Issue 10
10.3390/pharmaceutics13101584
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Article

Egr1 Gene Expression as a Potential Biomarker for In Vitro Prediction of Ocular Toxicity

by
Da-Bin Hwang
1,
Shin-Young Kim
1,
Dong-Hoon Won
1,
Changuk Kim
1,
Yoo-Sub Shin
1,
Jong-Hwan Park
2,
Young-Jin Chun
3,
Kyung-Min Lim
4,* and
Jun-Won Yun
1,5,*
1
Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Korea
2
Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
3
College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
4
College of Pharmacy, Ewha Womans University, Seoul 03760, Korea
5
Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon 14662, Korea
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2021, 13(10), 1584; https://doi.org/10.3390/pharmaceutics13101584
Submission received: 29 July 2021 / Revised: 9 September 2021 / Accepted: 28 September 2021 / Published: 29 September 2021
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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.
Keywords: early growth response-1; eye irritation; biomarker; reporter vector system; immortalized corneal cell early growth response-1; eye irritation; biomarker; reporter vector system; immortalized corneal cell
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MDPI and ACS Style

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. Egr1 Gene Expression as a Potential Biomarker for In Vitro Prediction of Ocular Toxicity. Pharmaceutics 2021, 13, 1584. https://doi.org/10.3390/pharmaceutics13101584

AMA Style

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. Egr1 Gene Expression as a Potential Biomarker for In Vitro Prediction of Ocular Toxicity. Pharmaceutics. 2021; 13(10):1584. https://doi.org/10.3390/pharmaceutics13101584

Chicago/Turabian Style

Hwang, Da-Bin, Shin-Young Kim, Dong-Hoon Won, Changuk Kim, Yoo-Sub Shin, Jong-Hwan Park, Young-Jin Chun, Kyung-Min Lim, and Jun-Won Yun. 2021. "Egr1 Gene Expression as a Potential Biomarker for In Vitro Prediction of Ocular Toxicity" Pharmaceutics 13, no. 10: 1584. https://doi.org/10.3390/pharmaceutics13101584

APA Style

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. (2021). Egr1 Gene Expression as a Potential Biomarker for In Vitro Prediction of Ocular Toxicity. Pharmaceutics, 13(10), 1584. https://doi.org/10.3390/pharmaceutics13101584

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