Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China.
Oxid Med Cell Longev. 2021 Feb 15;2021:6612689. doi: 10.1155/2021/6612689. eCollection 2021.
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.
and 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.
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 . 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 and .
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.
端粒沉默干扰因子 1 样蛋白（Dot1l）作为一种知名的甲基转移酶，在生物过程中发挥着重要作用。然而，其在单纯疱疹病毒 1 型（HSV-1）感染性角膜炎中的作用尚不清楚。
构建并评估了模型，以研究 Dot1l 在 HSV-1 诱导的角膜炎中的作用。用 HSV-1 感染 C57BL/6 小鼠角膜不同天数，并用或不用 Dot1l 抑制剂，以证明 Dot1l 在单纯疱疹性角膜炎（HSK）中的调控作用。培养人角膜上皮（HCE）细胞并感染 HSV-1，以确定涉及的分子机制。
在这项研究中，我们发现 Dot1l 与 HSK 呈正相关。用 EPZ004777（EPZ）抑制 Dot1l 可减轻角膜损伤，包括氧化应激和炎症。同样，用 EPZ 或小干扰 RNA（siRNA）抑制 Dot1l 可抑制 HSV-1 感染诱导的 HCE 细胞中的氧化应激和炎症。此外，我们的研究表明，HSV-1 感染后 HCE 细胞中 p38 MAPK 的表达升高，而抑制 Dot1l 可减少 HSV-1 感染诱导的 p38 MAPK 表达增加。
我们的研究结果表明，抑制 Dot1l 通过抑制 HSK 中 p38 MAPK 通路减少 ROS 产生，从而减轻角膜氧化应激和炎症。这些发现表明，Dot1l 可能是 HSK 的一个有价值的治疗靶点。
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