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臭氧暴露通过促进mtDNA泄漏和cGAS/STING激活来影响角膜上皮的命运

Kai Fan¹, Nuo Dong², Meichai Fang³

¹Eye Institute & Affiliated Xiamen Eye Center, School of Pharmaceutical Sciences & School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Pharmaceutical Sciences, and Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian 361102, China.

Journal of hazardous materials

|December 15, 2023

概括

臭氧暴露会损害眼睛表面,通过线粒体DNA泄漏和cGAS/STING通路激活引起角膜状转化. STING抑制有效地治疗了这些臭氧诱导的影响.

科学领域:

眼科医生眼科眼科
环境健康环境健康
分子生物学分子生物学

背景情况:

臭氧是影响人类健康的普遍空气污染物.
眼睛表面对臭氧的敏感性和潜在的机制在很大程度上是未知的.
了解臭氧对眼睛表面健康的影响对于公共健康至关重要.

研究的目的:

建立一个小鼠模型来研究臭氧暴露对眼睛表面和角膜上皮的影响.
阐明将臭氧暴露与角膜病理联系起来的分子机制.
为了确定臭氧引起的眼睛表面损伤的潜在治疗点.

主要方法:

开发一种控制臭氧暴露的小鼠模型.
对角膜上皮质恒常,分化和形态学的分析.
研究氧化损伤,线粒体DNA (mtDNA) 释放和cGAS/STING通路激活.
对下游NF-κB和TRAF6信号的评估.
选择性STING抑制剂 (C-176) 在预防和治疗臭氧诱导影响方面的评估.
三维成像分析角膜上皮层氨酸表达.

主要成果:

暴露在臭氧中破坏了角膜上皮质的稳态和分化,导致状转化.
臭氧诱导的氧化损伤和mtDNA的细胞质释放.
激活了cGAS/STING信号通路,随后激活了NF-κB和TRAF6通路.
暴露于臭氧会引起角膜炎症,并促进状转质形成.
使用C-176的STING抑制有效地预防和治疗角膜炎症和状转化症.
观察到异常的角膜上皮层角质蛋白表达模式.

结论:

臭氧暴露会通过 mtDNA 泄漏介导的 cGAS/STING 途径激活来诱导角膜状转化.
该cGAS/STING通路在臭氧诱导的角膜炎症和转化形成中发挥着关键作用.
STING抑制是臭氧引起的眼睛表面疾病的有前途的治疗策略.
这项研究为角膜状转化症和其他眼表面疾病提供了新的见解和潜在的治疗点.

关键词:

这就是CGAS/STING.MtDNADNA MtDNA是什么意思臭氧臭氧是什么?臭氧臭氧是什么状形质形成不全症.

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