Ferroptosis triggered by STAT1-IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury
文献类型：期刊论文
| 作者 | Kong, Peizhong10; Yang, Miaomiao8,9; Wang, Ying7; Yu, K. N.5,6; Wu, Lijun4 ; Han, Wei1,2,3,7,10
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| 刊名 | REDOX BIOLOGY
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| 出版日期 | 2023-10-01 |
| 卷号 | 66 |
| ISSN号 | 2213-2317 |
| 关键词 | Radiation-induced intestinal injury Ferroptosis Lipid peroxidation Arachidonic acid ACSL4 |
| DOI | 10.1016/j.redox.2023.102857 |
| 通讯作者 | Han, Wei(hanw@hfcas.ac.cn) |
| 英文摘要 | 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 and may result in termination of radiotherapy. At present, the pathogenesis of RIII has not been fully understood. Herein, we demonstrated that ferroptosis played a critical role in RIII occurrence. The RNA sequencing analysis strongly hinted ferroptosis was involved in RIII mice. In line with this, the levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), markers of lipid peroxidation, remarkably increased in RIII mice. And the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), improved the mice survival and alleviated intestinal fibrosis in vivo. Moreover, our results revealed that arachidonic acid (AA) enhanced ferroptosis in cultured intestinal epithelial cells (IECs) and organoids in vitro after irradiation, and AA gavage aggravated RIII in mice. Mechanistic studies revealed the level of ACSL4 protein significantly increased in mouse jejunums and IECs after irradiation. Radiation-induced ferroptosis in IECs was also prevented following ACSL4 knockdown or with the function inhibitor of ACSL4. Furthermore, we found that transcription of ACSL4 induced by irradiation was regulated by STAT1/IRF1 axis, and AMPK activation triggered by AA negatively regulated radiation-induced ferroptosis. Taken together, our results suggest that ferroptosis mediates RIII and reducing dietary AA intake as well as targeting the STAT1-IRF1-ACSL4 axis or AMPK may be the potential approaches to alleviate RIII. |
| WOS关键词 | ARACHIDONIC-ACID ; PELVIC RADIOTHERAPY ; CELL-DEATH ; STEM-CELLS ; IN-VITRO ; TARGET ; STAT1 |
| 资助项目 | Chinese National Natural Science Foundation[82102842] ; Chinese National Natural Science Foundation[81974484] ; Chinese National Natural Science Foundation[U20A20372] ; CASH-IPS Director's Fund[YZJJ2021QN39] ; CASH-IPS Director's Fund[YZJJ2022QN47] ; Key Research and Development Project of Anhui Province[202104j07020009] ; Hefei Comprehensive National Science Center ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | ELSEVIER |
| WOS记录号 | WOS:001070947600001 |
| 资助机构 | Chinese National Natural Science Foundation ; CASH-IPS Director's Fund ; Key Research and Development Project of Anhui Province ; Hefei Comprehensive National Science Center ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/132570]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Han, Wei |
| 作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, Inst Hlth & Med Technol, 350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China 2.Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215006, Peoples R China 3.Soochow Univ, Collaborat Innovat Ctr Radiat Med, Jiangsu Higher Educ Inst, Suzhou 215006, Peoples R China 4.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Peoples R China 5.City Univ Hong Kong, State Key Lab Marine Pollut, Kowloon Tong, Tat Chee Ave, Hong Kong 999077, Peoples R China 6.City Univ Hong Kong, Dept Phys, Kowloon Tong, Tat Chee Ave, Hong Kong 999077, Peoples R China 7.Chinese Acad Sci, Hefei Canc Hosp, Hefei 230031, Peoples R China 8.Anhui Publ Hlth Clin Ctr, Hefei 230011, Peoples R China 9.Anhui Med Univ, Affiliated Hosp 1, Hefei 230011, Peoples R China 10.Chinese Acad Sci, Anhui Prov Key Lab Med Phys & Technol, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei 230031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Peizhong,Yang, Miaomiao,Wang, Ying,et al. Ferroptosis triggered by STAT1-IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury[J]. REDOX BIOLOGY,2023,66. |
| APA | Kong, Peizhong,Yang, Miaomiao,Wang, Ying,Yu, K. N.,Wu, Lijun,&Han, Wei.(2023).Ferroptosis triggered by STAT1-IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury.REDOX BIOLOGY,66. |
| MLA | Kong, Peizhong,et al."Ferroptosis triggered by STAT1-IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury".REDOX BIOLOGY 66(2023). |
入库方式： OAI收割
来源：合肥物质科学研究院
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