Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea.
Primate Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeonbuk 56216, Korea.
Cells. 2019 Sep 6;8(9):1042. doi: 10.3390/cells8091042.
Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.
辐射暴露导致的肝损伤，无论是意外的还是由于治疗引起的，都可能导致肝功能障碍。目前，放射疗法被用于治疗各种癌症，包括肝细胞癌；然而，由于肝脏对辐射的耐受性差，治疗剂量受到限制。此外，目前还没有可靠的生物标志物来预测肝损伤及其相关副作用。在这里，我们研究了辐射暴露后肝脏和血浆中纤维蛋白原样 1（FGL1）的表达。我们发现，30Gy 的肝脏照射（IR）诱导细胞死亡，包括凋亡、坏死和自噬，在小鼠的急性和亚急性阶段发生肝脏纤维化变化。此外，IR 后肝脏中 FGL1 的表达模式与损伤相关蛋白和氧化应激标志物所代表的肝损伤有关。我们通过暴露于人肝细胞来证实 FGL1 表达与肝细胞损伤之间的关联。为了确定其作为辐射诱导肝损伤潜在生物标志物的适用性，我们测量了全身照射（TBI）或肝脏 IR 后小鼠肝脏组织和血浆中的 FGL1。在 TBI 中，与其他主要内部器官（包括心脏、肺、肾和肠）相比，FGL1 在肝脏中的升高幅度最高。值得注意的是，血浆 FGL1 与肝脏 IR 的辐射剂量具有良好的相关性。我们的数据表明，FGL1 的上调表明肝脏对 IR 的反应性肝细胞损伤。这些结果表明，血浆 FGL1 可能代表急性和亚急性肝脏辐射暴露的潜在生物标志物。
