Interferon regulatory factor 1-triggered free ubiquitin protects the intestines against radiation-induced injury via CXCR4/FGF2 signaling

  • MedComm (2020). 2022 Aug 26;3(3):e168. doi: 10.1002/mco2.168.
Yang Jiao  1  2 ,  Jing Xu  1  2 ,  Bin Song  3 ,  Ailing Wu  4 ,  Lu Pan  1  2 ,  Ying Xu  1  2 ,  Fenghao Geng  4 ,  Xiaoqian Li  5 ,  Congzhao Zhao  1  2 ,  Min Hong  1  2 ,  Xuanyu Meng  1  2 ,  Judong Luo  6 ,  Pengfei Liu  1 ,  Ming Li  1  2 ,  Wei Zhu  1  2 ,  Jianping Cao  1  2 ,  Shuyu Zhang  3  4  5  6  7
Affiliations
  • 1. School of Radiation Medicine and Protection Medical College of Soochow University Suzhou China.
  • 2. State Key Laboratory of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University Suzhou China.
  • 3. Laboratory of Radiation Medicine West China Second University Hospital Sichuan University Chengdu China.
  • 4. Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 Hospital Chengdu China.
  • 5. West China School of Basic Medical Sciences & Forensic Medicine Sichuan University Chengdu China.
  • 6. Department of Oncology The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University Changzhou China.
  • 7. NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital Mianyang China.
PMID: 36051984 DOI: 10.1002/mco2.168
Abstract

Radiation-induced intestinal injury is a serious concern during abdominal and pelvic cancers radiotherapy. Ubiquitin (Ub) is a highly conserved protein found in all eukaryotic cells. This study aims to explore the role and mechanism of free Ub against radiogenic intestinal injury. We found that free Ub levels of irradiated Animals and human patients receiving radiotherapy were upregulated. Radiation-induced Ub expression was associated with the activation of interferon regulatory factor 1 (IRF1). Intraperitoneal injection of free Ub significantly reduced the mortality of mice following 5-9 Gy total body irradiation (TBI) through the Akt pathway. Free Ub facilitates small intestinal regeneration induced by TBI or abdominal irradiation. At the cellular level, free Ub or its mutants significantly alleviated cell death and enhanced the survival of irradiated intestinal epithelial cells. The radioprotective role of free Ub depends on its receptor CXCR4. Mechanistically, free Ub increased fibroblast growth factor-2 (FGF2) secretion and consequently activated FGFR1 signaling following radiation in vivo and in vivo. Thus, free Ub confers protection against radiation-induced intestinal injury through CXCR4/Akt/FGF2 axis, which provides a novel therapeutic option.

Keywords
fibroblast growth factor‐2; free ubiquitin; ionizing radiation; radiation‐induced intestinal injury.
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