线粒体损伤会通过基胺诱导囊炎的cGAS-STING信号引起炎症
Jinji Chen1, Shengsheng Liang1, Cheng Li1
1Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
概括
线粒体损伤释放DNA,激活cGAS-STING通路并引起胺诱导的囊炎. 阻止STING可以减少炎症,这表明它是这种疾病的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 线粒体功能障碍释放线粒体DNA (mtDNA),激活cGAS-STING通路并促进炎症.
- 诸如氧化应激,病毒感染和药物毒性等因素可以诱导线粒体损伤.
- 胺诱导性囊炎 (KC) 涉及炎症途径,mtDNA可能发挥关键作用.
研究的目的:
- 通过cGAS-STING通路调查线粒体DNA (mtDNA) 作为胺诱导囊炎 (KC) 中炎症调解者的作用.
- 评估cGAS和STING在KC和体外细胞模型的老鼠模型中的表达.
- 探索针对KC中的cGAS-STING通路的治疗潜力.
主要方法:
- 在暴露于胺胺的老鼠膀组织和SV-HUC-1细胞中评估cGAS和STING表达.
- 使用传输电子显微镜检查线粒体形态.
- 使用qPCR测量了反应性氧物种 (ROS) 和量化炎症因子/细胞因子.
主要成果:
- 胺提升了cGAS和STING表达在体内和体外.
- 斯廷抗击抑制了NF-κB p65和IRF3的核转位,减少了炎症性细胞因子 (IL-6,IL-8,CXCL10).
- 胺诱导的线粒体损伤释放了mtDNA,在耗尽后,抑制了cGAS-STING通路;mtDNA重新引入部分恢复了炎症.
结论:
- 在KC中确认了cGAS-STING通路的激活,并证明了线粒体损伤.
- 突出了cGAS-STING途径在KC病变发生过程中的关键作用.
- 建议cGAS-STING通路作为KC的潜在治疗标.
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