期刊
CELL DEATH & DISEASE
卷 11, 期 2, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-020-2299-1
关键词
-
类别
资金
- National Natural Science Foundation of China [U1501224, 81800458, 81700536]
- Natural Science Foundation Team Project of Guangdong Province [2018B030312009]
- Science and Technology Developmental Special Foundation of Guangdong Province [2017B020226003]
Ferroptosis has recently emerged as an iron-dependent form of nonapoptotic cell death, which is also a regulated necrosis process and a response to tumor suppression. However, whether ferroptosis is involved in ulcerative colitis (UC) is unknown. The aims of this study were to investigate whether the ferroptosis is involved in UC, particularly intestinal epithelial cell (IEC) death, and to analyze the effect of the nuclear factor kappa Bp65 subunit (NF-kappa Bp65) on ferroptosis. The gene expression of ferroptosis-related proteins was assessed in intestinal mucosal samples from human UC. The experimental model of UC was induced with dextran sulfate sodium (DSS). Ferroptosis of IECs was evaluated, the effect of NF-kappa Bp65 on ferroptosis was analyzed by using IEC-specific NF-kappa Bp65-deleted mice (p65(IEC-KO)), and the ferroptosis signaling pathway was investigated in vitro and in vivo. The results showed that ferroptosis was significantly induced in the IECs from UC patients and mice with colitis, and the ferroptosis was mediated by endoplasmic reticulum (ER) stress signaling. The specific deletion of IEC NF-kappa Bp65 clearly upregulated ferroptosis and exacerbated colitis, and the result showed that phosphorylated-NF-kappa Bp65 significantly inhibited ER stress signaling by directly binding eukaryotic initiation factor 2 alpha. These data indicate that ferroptosis contributes to UC via ER stress-mediated IEC cell death, and that NF-kappa Bp65 phosphorylation suppresses ER stress-mediated IEC ferroptosis to alleviate UC. The results suggest that ferroptosis involves in IEC death in UC, NF-kappa Bp65 play a critical role in the ferroptotic inhibition, and ferroptosis is a potential therapeutic target for UC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据