Ferroptosis triggered by STAT1- IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury

• DOI: 10.1016/j.redox.2023.102857
• Publication Date: 2023-08-18T12:10:24Z
• Authors: Peizhong Kong; Miaomiao Yang; Ying Wang; K.N. Yu; Lijun Wu; Wei Han
• Keywords: GPX4; Malondialdehyde

Radiation-induced intestinal injury (RIII), a common gastrointestinal complication caused by radiotherapy on pelvic, abdominal and retroperitoneal tumors, seriously affects the life quality of patients may result in termination radiotherapy. At present, pathogenesis RIII has not been fully understood. Herein, we demonstrated that ferroptosis played critical role occurrence. The RNA sequencing analysis strongly hinted was involved mice. In line with this, levels 4-hydroxynonenal (4-HNE) malondialdehyde (MDA), markers lipid peroxidation, remarkably increased And inhibitor, Ferrostatin-1 (Fer-1), improved mice survival alleviated fibrosis vivo. Moreover, our results revealed arachidonic acid (AA) enhanced cultured epithelial cells (IECs) organoids vitro after irradiation, AA gavage aggravated Mechanistic studies level ACSL4 protein significantly mouse jejunums IECs irradiation. also prevented following knockdown or function inhibitor ACSL4. Furthermore, found transcription induced irradiation regulated STAT1/IRF1 axis, AMPK activation triggered negatively radiation-induced ferroptosis. Taken together, suggest mediates reducing dietary intake as well targeting STAT1-IRF1-ACSL4 axis be potential approaches to alleviate RIII.