铁失调和铁与肺纤维化有关:来自异常性肺纤维化,全身性硬化和COVID-19患者的见解
Shuai Jiang1, Xiangguang Shi2, Xiangzhen Kong3
1Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China.
概括
肺纤维化 (PF),包括COVID-19和全身性硬化相关的PF中常见的是铁过载和铁. 这些在肺细胞和巨细胞中特别明显的过程代表了PF的有前途的治疗点.
科学领域:
- 肺部医学
- 细胞生物学
- 免疫学
背景情况:
- 肺纤维化 (PF) 是主要的死亡原因,通常与炎症和组织损伤有关.
- 铁代谢和铁死在各种PF疾病中的作用尚未完全理解.
- 研究铁在不同类型的PF中的作用对于了解疾病机制至关重要.
研究的目的:
- 在异常性肺纤维化 (IPF),全身性硬化相关性肺纤维化 (SSc-PF) 和COVID-19中比较铁代谢和铁化特征.
- 调查细胞局部化和针对PF中铁过载和铁的治疗潜力.
- 通过公开数据集和体外/体内模型验证发现.
主要方法:
- 在IPF,SSc-PF和COVID-19患者样本中比较铁含量 (珍珠染色,费里丁) 和铁标记 (MDA,4HNE,GPX4,FSP1).
- 免疫组织化学,传输电子显微镜,以及用于检测铁的公共数据集分析.
- 使用SARS-CoV-2尖端蛋白诱导的PF模型进行体外和体内研究,评估铁介导的炎症和纤维化与deferoxamine (DFO) 和Ferrostatin-1 (Fer1).
主要成果:
- COVID-19 呈现出最严重的肺损伤和纤维化.
- 在IPF,SSc-PF和COVID-19中,铁过载和铁是普遍存在的,COVID-19中铁代谢的特征不同 (HO-1较高).
- 铁过载和铁主要发生在膜II型细胞和巨细胞中;DFO和Fer1治疗减少了体内纤维化和炎症标志物 (MDA,IL-6).
结论:
- 铁过载和铁是各种形式的肺纤维化的常见病理特征.
- 针对铁代谢和铁的途径为肺纤维化提供了潜在的治疗策略.
- 这些发现突显了铁依赖细胞死亡在PF病变中的保留作用.
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