Protective Effect of IGFBP-3 Protein on Heavy Ion Radiation Induced Injury in Mice

Manned spaceflight and nuclear technology applications are running on a highway in China today. The radiation and nuclear safety will continue to be a major national demand in a long term. Thus, the continuous observation of new radiation protection molecular targets and related drugs is of great value to us. Our previous study has found that the circulating Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) in blood of mice showed a significant increase after total body irradiation by ionizing radiation. However, the function of IGFBP-3 and the effects of its blood level change on radiation induced damages are still unclear. In this study, we set up the Igfbp3 gene overexpression and knock-down cell models in mouse Kupffer (MKC) cells. The CCK-8 assay, EdU assay, clone formation assay and microsphere phagocytosis experiment were performed for detection of the proliferation activity, DNA replication activity and phagocytic ability of different cell models after carbon-ion irradiation. Moreover, mice were tail vein injected with recombinant IGFBP-3 protein at 2 hours before 5 Gy (lethal dose) carbon-ion irradiation to elevate the blood IGFBP-3 protein level, and the survival curves of mice were drawn. The results demonstrated that overexpression of IGFBP-3 protein significantly enhanced DNA replication activity, cell viability, clone formation rate, and phagocytic ability towards microspheres in MKC cells after radiation exposure. On the contrary, the knock-down of IGFBP-3 protein expression reduced the above results. Injection of IGFBP-3 protein before carbon-ion exposure significantly delayed the time of death in mice. Our results indicate at the cellular and animal levels that IGFBP-3 protein has the potential to mitigate radiation-induced damages and serve as a target for radiation protection. Through enhancing the radiation resistance and phagocytic ability of Kupffer cells in mice to reduce the risk of infection after radiation exposure might be the underlying mechanism of the effects of IGFBP-3 on radiation protection.