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Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2021 (2021)
- Publication Year :
- 2021
- Publisher :
- Hindawi, 2021.
-
Abstract
- Background. Disruptor of telomeric silencing 1-like (Dot1l) plays a vital role in biological processes as a well-known methyltransferase. However, its role in herpes simplex virus type 1- (HSV-1-) infected keratitis remains unclear. Methods. In vitro and in vivo models were assessed to investigate the role of Dot1l in HSV-1 induced keratitis. C57BL/6 mice corneas were infected with HSV-1 for different days, with or without Dot1l inhibitor, to demonstrate the regulation of Dot1l in herpes simplex keratitis (HSK). Human corneal epithelial (HCE) cells were cultured and infected with HSV-1 to identify the molecular mechanisms involved. Results. In this study, we found that Dot1l was positively related to HSK. Inhibition of Dot1l with EPZ004777 (EPZ) alleviated corneal injury, including oxidative stress and inflammation in vivo. Similarly, the inhibition of Dot1l with either EPZ or small interfering RNA (siRNA) showed an inhibitory effect on HSV-1-induced oxidative stress and inflammation in HCE cells. Moreover, our study revealed that the expression of p38 MAPK was elevated after HSV-1 infection in HCE cells, and the inhibition of Dot1l could reduce the increased expression of p38 MAPK induced by HSV-1 infection in vivo and in vitro. Conclusion. Our results demonstrated that the inhibition of Dot1l alleviated corneal oxidative stress and inflammation by inhibiting ROS production through the p38 MAPK pathway in HSK. These findings indicated that Dot1l might be a valuable therapeutic target for HSK.
- Subjects :
- Male
Aging
Small interfering RNA
Article Subject
p38 mitogen-activated protein kinases
Inflammation
Herpesvirus 1, Human
medicine.disease_cause
Biochemistry
p38 Mitogen-Activated Protein Kinases
Keratitis
In vivo
medicine
Animals
Protein Kinase Inhibitors
QH573-671
Chemistry
Epithelium, Corneal
Cell Biology
General Medicine
Histone-Lysine N-Methyltransferase
medicine.disease
In vitro
Enzyme Activation
Mice, Inbred C57BL
Oxidative Stress
Herpes simplex virus
Cancer research
Keratitis, Herpetic
sense organs
medicine.symptom
Cytology
Oxidative stress
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19420900
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....63691a8883f487be519e8cfe6edd3ff3
- Full Text :
- https://doi.org/10.1155/2021/6612689