Anwar Khandaker N, Soleimani Mohammad, Ashraf Mohammad Javad, Moghtader Amirhossein, Koganti Raghuram, Ghalibafan Seyyedehfatemeh, Baharnoori Mahbod, Arabpour Zohreh, Cheraqpour Kasra, Sebhat Aron M, Abtahi Mansour, Yao Xincheng, Ghassemi Mahmood, Djalilian Ali R
Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA.
Department of Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60607, USA.
Cells. 2024 Dec 6;13(23):2021. doi: 10.3390/cells13232021.
Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways-particularly mitogen-activated protein kinase (MAPK) signaling-in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal-limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy.
芥子气角膜病变（MGK）是接触硫芥子气后的一种并发症，是一种致盲性眼表疾病，涉及关键细胞途径，包括细胞凋亡、氧化应激和炎症。最近的研究表明，细胞衰老参与了芥子气毒性的病理生理过程。本研究旨在评估衰老和应激相关途径，特别是丝裂原活化蛋白激酶（MAPK）信号通路在氮芥（NM）诱导的角膜损伤中的作用。在体外，将原代人角膜上皮细胞（P-HCECs）、原代人角膜间充质基质细胞（hcMSCs）和人角膜缘上皮细胞（HCLE）系暴露于不同浓度的NM中。结果显示细胞衰老呈剂量依赖性增加，表现为Ki67表达降低、p16和p21 mRNA水平升高，以及MAPK途径激活。用选择性p38-MAPK抑制剂处理可显著降低衰老标志物水平，并改善NM暴露后的细胞增殖。总体而言，这些研究表明，NM暴露会触发细胞衰老和应激相关的MAPK信号通路，而p38-MAPK抑制可减轻这些影响，提示了一种潜在的治疗策略。
