Proteomic analysis of the survival effect of TPO receptor agonist Romiplostim treatment in mice exposed to a lethal dose of radiation

Background: The thrombopoietin receptor agonist romiplostim (RP) is a therapeutic agent for immune thrombocytopenia that can achieve complete survival in mice exposed to a lethal dose of ionizing radiation. The estimated mechanism of the radio-protective/mitigative effects of RP has been proposed; however, the detailed mechanism of action remains unclear. The present study aimed to elucidate the mechanism of the radio-protective/mitigative effects of RP, the fluctuation of protein in the blood was analyzed by proteomics. Methods: Peripheral blood was harvested from the fundus of mice treated with non-total body irradiation (TBI) and 7 Gy TBI with or without the administration of RP on days 10 and 18 after TBI. Serum prepared from each treated mouse was analyzed using a Liquid Chromatograph-tandem Mass Spectrometer. Results: Eleven proteins were identified by proteomics methods from 269 analyzed proteins detected in mice exposed to a lethal dose of TBI. Many proteins were found to be involved in cell death and liver damage. Conclusions: It was suggested that the effect of RP in reducing radiation damage may be largely related to the suppression of cell death and liver damage.