FG-4592 alleviates radiation-induced intestinal injury by facilitating recovery of intestinal stem cell and reducing damage of intestinal epithelial

• DOI: 10.1016/j.toxlet.2021.12.011
• Publication Date: 2021-12-17T16:49:57Z
• Authors: Penglin Xia; Yajie Yang; Ruling Liu; Zhenlan Feng; Yuhan Lin; Haibo Tang; Jicong Du; Ying Cheng; Jianming Cai; Hao Hu; Cong Liu; Xiaohua Xu; Hu Liu
• Keywords: Intestinal epithelium; Hypoxia; Intestinal Disorder

Damage of Intestinal Stem Cells (ISCs) is the main cause of radiation induced-intestinal injury (RIII). Recently, hypoxia Inducible factor (HIF) was verified to be critical for promoting proliferation of ISCs, which suggested a protective role of HIF in the RIII. Thus, we investigated the effect of FG-4592, a novel up-regulator of HIF, on the protection of RIII. With/without FG-4592 treatment, the abdomen of mice was radiated, and intestinal injury was assessed. Especially, by intestinal organoid culture, the multiplication capacity and differentiation features of ISCs were detected. As a result, FG-4592, a novel up-regulator of HIF could remit RIII and promote regeneration and differentiation of ISCs after radiation, which were depended on HIF-2 rather than HIF-1.