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

Subjects: Physics >> Nuclear Physics Subjects: Biology >> Radiobiology submitted time 2024-05-06

ZHOU Yumeng CAI Shufan BAI Hao WANG Jufang WEI Wenjun YANG Mingjun

Abstract： 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) showed a significant increase after total body exposure of mice to ionizing radiation. However, the function of IGFBP-3 and the effects of it 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 investing 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 carbon-ion irradiation, and the survival curves of mice were drawn. The results showed that overexpression of IGFBP-3 protein significantly alleviated the radiation-induced decrease of the DNA replication activity, cell viability, clone formation rate, and phagocytic ability of MKC cells. 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 reduce 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.

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