噬铁激活状态决定骨髓和脾脏巨噬细胞对铁凋亡的易感性。

IF 10 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI:10.7150/ijbs.114545
Xin Lai, Aimin Wu, Yao Liu, Chen Liu, Junzhou Chen, Ke Gu, Bing Yu, Hui Yan, Junqiu Luo, Ping Zheng, Jie Yu, Daiwen Chen
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引用次数: 0

摘要

巨噬细胞表现出异质性,因为它们存在于不同的组织中,具有不同的细胞命运。铁下垂是细胞命运的一种,但不同类型巨噬细胞对铁下垂的敏感性及相关分子机制尚不清楚。本研究探讨了骨髓和脾巨噬细胞对铁凋亡的敏感性,重点探讨了铁蛋白吞噬的贡献。我们发现骨髓M2巨噬细胞更容易发生铁凋亡,这是由于与脾巨噬细胞相比,骨髓M2巨噬细胞的溶质载体家族40成员1 (SLC40A1)和铁蛋白重/轻链(FTH/L)表达较低,不稳定铁水平较高。此外,利用自噬通量调节剂和自噬相关5 (ATG5)和核受体共激活因子4 (NCOA4)敲除的RAW264.7细胞进行的实验证明,铁蛋白自噬激活,特别是在M2巨噬细胞中,被确定为不稳定铁水平增加的主要原因。这些结果为进一步了解巨噬细胞的异质性和功能提供了新的方向,并为巨噬细胞调节起关键作用的各种健康问题提供了创新的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ferritinophagy activation states determine the susceptibility to ferroptosis of macrophages in bone marrow and spleen.

Macrophages exhibit heterogeneity due to their presence in different tissues that have distinct cell fates. Ferroptosis is one type of cellular fate, but the sensitivity of different types of macrophages to ferroptosis and the associated molecular mechanisms are not clear. This study explored the ferroptosis sensitivity of bone marrow and splenic macrophage, focusing on the contribution of ferritinophagy. We found that bone marrow M2 macrophages were more susceptible to ferroptosis, which was attributed to their lower solute carrier family 40 member 1 (SLC40A1) and ferritin heavy/light chain (FTH/L) expression and higher labile iron levels compared to those of splenic macrophages. Further, ferritinophagy activation, particularly in M2 macrophages, was identified as the primary cause of increased labile iron levels, as evidenced by experiments using autophagic flux modifiers and RAW264.7 cells with autophagy related 5 (ATG5) and nuclear receptor coactivator 4 (NCOA4) knockdown and NCOA4 knockout. These results provide a new direction for further understanding the heterogeneity and functionality of macrophages, and offers innovative treatments for a variety of health issues in which macrophage regulation plays a critical role.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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