在辐射皮肤炎中,NCOA4-介导的铁死驱动cGAS-STING-依赖性炎症:通过Cu-ATSM进行保护性调制
Shuai Li1, Letaotao Chen2, Zeyu Fang1
1Department of Emergency, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, Zhejiang-Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory, Wenzhou Key Laboratory of Basic Science and Translational Research of Radiation Oncology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Free radical biology & medicine
|February 25, 2026
概括
辐射性皮肤炎涉及铁,一种依赖于铁的细胞死亡,与通过NCOA4-ferroptosis-cGAS-STING通路的免疫激活有关. 化合物Cu-ATSM通过抑制铁亡和相关炎症,有效地减轻这种皮肤损伤.
科学领域:
- 转毒生物学 转毒生物学
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 放射性皮肤炎 (RD) 是一种常见的放射治疗并发症,其分子驱动因素不明.
- 铁亡,一种受调节的细胞死亡形式,涉及到组织损伤,但其在RD和皮肤炎症中的作用尚不确定.
研究的目的:
- 研究NCOA4介导的费里丁的作用及其与辐射皮肤炎中cGAS-STING通路的相互作用.
- 评估Cu-ATSM在减轻辐射引起的皮肤损伤方面的治疗潜力.
主要方法:
- 集成的多组学,细胞共同培养,计算建模和体内验证.
- 在被辐射的角质细胞和巨细胞中分析了铁和炎症标志物.
- 在试验室和小鼠RD模型中测试了Cu-ATSM.
主要成果:
- 电离辐射诱导了NCOA4介导的角质细胞中的铁亡,释放DAMP,激活了巨细胞中的cGAS-STING-IFN-β轴.
- Cu-ATSM抑制了铁和STING激活,作为NCOA4.4的竞争性抑制剂.
- 局部Cu-ATSM治疗改善了RD严重程度,降低了ferroptosis,并在体内减少了炎症性细胞因子.
结论:
- 在RD中,NCOA4-ferroptosis-cGAS-STING轴是关键途径,将氧化还原失衡与炎症联系起来.
- Cu-ATSM通过抑制ferroptosis和ferroptosis驱动的免疫激活来证明多式治疗效果.
- Cu-ATSM是一种有前途的治疗策略,用于辐射引起的皮肤损伤.
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