Dang Dan, Zhang Chuan, Meng Zhaoli, Lv Xiaoming, Li Zhenyu, Wei Jiaqi, Wu Hui
Department of Neonatology, First Hospital of Jilin University, Changchun 130021, China.
Department of Pediatric Surgery, First Hospital of Jilin University, Changchun 130021, China.
iScience. 2022 Oct 19;25(11):105406. doi: 10.1016/j.isci.2022.105406. eCollection 2022 Nov 18.
Multiple types of regulated cell death (RCD) have been demonstrated to cause gut barrier dysfunction in necrotizing enterocolitis (NEC); however, whether and how ferroptosis is involved in NEC remains unknown. Here, ferroptosis was identified to play a role in NEC using bioinformatics analyses and wet experiments. Inhibition of ferroptosis significantly alleviated NEC in newborn mice. expression levels were augmented and positively correlated with ferroptosis in NEC. Surprisingly, was critically correlated with multiple types of RCD, including autophagy, apoptosis and pyroptosis, as well as hypoxia and inflammation. Besides, was positively correlated with the abundance of multiple types of immune cells, including macrophage, activated dendritic cell, neutrophil and regulatory T cell. Conclusively, we first identified the involvement and role of ferroptosis in NEC and revealed the potential effects of on immune disorders, which could provide a rationale for future research on ferroptosis in NEC.
多种类型的程序性细胞死亡(RCD)已被证明会导致坏死性小肠结肠炎(NEC)中的肠道屏障功能障碍;然而,铁死亡是否以及如何参与NEC仍不清楚。在这里,通过生物信息学分析和湿实验确定铁死亡在NEC中起作用。抑制铁死亡可显著减轻新生小鼠的NEC。[此处原文缺失相关蛋白或分子名称]的表达水平升高,且与NEC中的铁死亡呈正相关。令人惊讶的是,[此处原文缺失相关蛋白或分子名称]与多种类型的RCD密切相关,包括自噬、凋亡和焦亡,以及缺氧和炎症。此外,[此处原文缺失相关蛋白或分子名称]与多种类型免疫细胞的丰度呈正相关,包括巨噬细胞、活化的树突状细胞、中性粒细胞和调节性T细胞。总之,我们首次确定了铁死亡在NEC中的参与情况和作用,并揭示了[此处原文缺失相关蛋白或分子名称]对免疫紊乱的潜在影响,这可为未来NEC中铁死亡的研究提供理论依据。