在辐射诱导的肺纤维化进展中的铁亡相关的细胞外矩阵重塑
Xinyu Yan1,2, Peixuan Yang1,2, Chen Yang1,2
1Zhongshan City People's Hospital, Xinxiang Medical University, Xinxiang, China.
Dose-response : a publication of International Hormesis Society
|October 1, 2024
概括
辐射诱导性肺纤维化 (RILF) 涉及铁亡,这是一个细胞死亡过程. 经受铁亡的纤维细胞可能通过释放细胞外基质 (ECM) 来加速肺纤维化,这表明铁亡是治疗标.
科学领域:
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
- 在瘤学瘤学.
背景情况:
- 辐射诱导性肺纤维化 (RILF) 是胸部放射治疗的严重并发症.
- 铁亡,一种独特的细胞死亡形式,与RILF的病变产生有关.
- 精确的机制和细胞对RILF中铁亡的贡献仍然不清楚.
研究的目的:
- 为了阐明RILF中铁灭的机制.
- 为了确定在RILF进展期间参与铁亡的特定细胞类型.
- 为了研究铁亡和细胞外基质 (ECM) 沉积之间的联系.
主要方法:
- 对RILF肺组织进行了组织病理学分析 (H&E,马森染色).
- 免疫组织化学 (IHC) 用于铁亡标志物 (GPX4,ACSL4,NCOA4).
- 从转录组数据分析与铁亡相关的基因 (FRG) 和途径得分;单细胞RNA测序 (sc-RNAseq) 和免疫光 (IF) 进行细胞类型特定分析.
主要成果:
- 在被辐射的肺部观察到,ACSL4和NCOA4升高,GPX4降低.
- 在RILF转录组数据中,FRG分数和纤维化途径之间的正相关性.
- 肌纤维细胞中FRG和ECM评分的升级;纤维细胞区域中PDGFR-α和ACSL4的同定位.
结论:
- 在RILF中经历铁亡的纤维细胞可能会增加ECM释放,加剧肺纤维化.
- 铁化成为缓解RILF的潜在治疗点.
- 了解细胞类型特异性铁亡对于RILF治疗策略至关重要.
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