Identification of the Kupffer cell-derived circulating IGFBP-3 as a universal radiation biomarker for heavy ion, proton, and X-ray exposure

Hao Bai; Jufang Wang; Qiaojuan Wang; Yaxiong Chen; Guoying Miao; Tongshan Zhang; Junrui Hua; Yanan Zhang; Jinpeng He; Nan Ding; Heng Zhou; Li Sui; Wenjun Wei

doi:10.1016/j.ecoenv.2023.115526

Identification of the Kupffer cell-derived circulating IGFBP-3 as a universal radiation biomarker for heavy ion, proton, and X-ray exposure

Ecotoxicol Environ Saf. 2023 Oct 15:265:115526. doi: 10.1016/j.ecoenv.2023.115526. Epub 2023 Sep 26.

Authors

Hao Bai¹, Jufang Wang¹, Qiaojuan Wang², Yaxiong Chen¹, Guoying Miao³, Tongshan Zhang¹, Junrui Hua⁴, Yanan Zhang⁴, Jinpeng He¹, Nan Ding¹, Heng Zhou¹, Li Sui⁵, Wenjun Wei⁶

Affiliations

¹ Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China; National Innovation Center of Radiation Application, Beijing 102413, China.
³ Department of Radiotherapy, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China.
⁴ Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
⁵ Department of Nuclear Physics, China Institute of Atomic Energy, Beijing 102413, China; National Innovation Center of Radiation Application, Beijing 102413, China. Electronic address: lisui@ciae.ac.cn.
⁶ Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: weiwenjun@impcas.ac.cn.

PMID: 37769581
DOI: 10.1016/j.ecoenv.2023.115526

Abstract

The minimally invasive biomarkers that can facilitate a rapid dose assessment are valuable for the early medical treatment when accidental or occupational radiation exposure happens. Our previous proteomic research identified one kind of circulating protein, Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), which showed a significant increase after total body exposure of mice to carbon ions and X-rays. However, several critical issues such as the responses to diverse radiation, the origin and underlying mechanism in radiation response obstruct the utilization of circulating IGFBP-3 as a reliable radiation biomarker. In this study, mice were subjected to total or partial body irradiation with carbon ions, protons or X-rays, or treated with chloroform as a comparison. The level of IGFBP-3 in serum and different organs were measured via Enzyme Linked Immunosorbent Assay (ELISA), Western blot (WB) and Immunohistochemistry (IHC). A significant increase of IGFBP-3 was discovered in serum and liver tissue post-irradiation with three kinds of radiation, but absent when challenged with chloroform. Likewise, a similar response was also observed in blood samples from patients receiving radiotherapy. Moreover, the effect of radiation on three main hepatic cells was investigated, the findings indicated that IGFBP-3 could be detected in the culture medium of Kupffer cells (MKC) alone and was elevated in cells and cultured medium of MKC post-irradiation. Additionally, we observed a co-expression effect between P53 and IGFBP-3 in liver tissues and MKC post-irradiation. Along with down-regulation of Trp53 by siRNA, the response of IGFBP-3 to radiation was attenuated. The present study demonstrated that circulating IGFBP-3 could be a promising universal biomarker for complex environmental radiation exposure, and the upregulation of IGFBP-3 is attributed to the MKC in a P53-dependent manner. Circulating IGFBP-3 assays would offer rapid, convenient and effective dose and toxicity assessment methods in occupational exposure or radiation disaster management.

Keywords: Biomarker; Circulating IGFBP-3; Ionizing radiation; Kupffer cells; P53; Radiation safety.