1,2-propanediol ameliorated radiation-induced intestinal injury in mice via regulating P53

Radiotherapy is constricted by collateral normal tissue injury during treatment, particularly the gastrointestinal tracts, which is usually referred as radiation-induced gastrointestinal syndrome (RIGS). Currently, there is no FDA-approved agent for the prevention or treatment of RIGS. By using a mice model of RIGS, we demonstrated that 1,2-propanediol (1,2-PD) prevents radiation-induced fatal intestinal injury and significantly increases mice survival following lethal doses of radiation. 1,2-PD pretreatment also enhanced the survival of Lgr5 ⁺ ISCs and improved crypts regeneration after radiation. Moreover, we confirmed 1,2-PD induces dormant cell cycle arrest in enterocytes and ameliorates DNA damage both in vitro and in vivo. 1,2-PD pretreatment specifically blocked crypt apoptosis via inhibiting P53-PUMA signal pathway. We also proved that P53 deficiency aggravated intestinal injury and impaired the intestinal radioprotection of 1,2-PD. These results demonstrate that ISCs play a key role in radiation-induced intestinal regeneration and that 1,2-PD acts as a potent intestinal radioprotector by promoting resting of intestinal crypt cells and blocking P53-PUMA mediated crypt apoptosis after irradiation.