| First Author | Xu M | Year | 2020 |
| Journal | Cell Death Dis | Volume | 11 |
| Issue | 2 | Pages | 86 |
| PubMed ID | 32015337 | Mgi Jnum | J:302367 |
| Mgi Id | MGI:6508214 | Doi | 10.1038/s41419-020-2299-1 |
| Citation | Xu M, et al. (2020) Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis. Cell Death Dis 11(2):86 |
| abstractText | 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-kappaBp65) 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-kappaBp65 on ferroptosis was analyzed by using IEC-specific NF-kappaBp65-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-kappaBp65 clearly upregulated ferroptosis and exacerbated colitis, and the result showed that phosphorylated-NF-kappaBp65 significantly inhibited ER stress signaling by directly binding eukaryotic initiation factor 2alpha. These data indicate that ferroptosis contributes to UC via ER stress-mediated IEC cell death, and that NF-kappaBp65 phosphorylation suppresses ER stress-mediated IEC ferroptosis to alleviate UC. The results suggest that ferroptosis involves in IEC death in UC, NF-kappaBp65 play a critical role in the ferroptotic inhibition, and ferroptosis is a potential therapeutic target for UC. |
