FG‐4592 protected haematopoietic system from ionising radiation in mice

Abstract Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG‐4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG‐4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA‐sequence technique (RNA‐Seq) was conducted to explore the mechanism of FG‐4592 in the haematopoietic system. Our results indicated that FG‐4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR‐induced injury. The number of BMCs was increased and protected against IR‐induced apoptosis. FG‐4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA‐Seq and Western blot showed that the NF‐κB signalling pathway and hypoxia‐inducible factor‐1 (HIF‐1) signalling pathway were upregulated by FG‐4592. Meanwhile, RT‐PCR results showed that FG‐4592 could promote inflammatory response significantly. FG‐4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF‐κB, HIF signalling pathway.