我们的研究发现，细胞外游离泛素不仅与放射损伤和组织放射敏感性密切相关，且具有减轻放射损伤的作用。作为细胞外环境的信号受体，CXCR4跨膜受体蛋白能穿越细胞膜，将胞外信号传递到细胞内。本项目，我们将放射敏感性不同且具有重要生物效应的皮肤、肺和肠组织/细胞作为研究对象，通过提高/降低胞外游离泛素水平，观察其对放射敏感性不同的组织/细胞的放射损伤的影响；通过抑制/下调CXCR4表达以及抑制MAPK/ERK和/或PI3K/AKt信号通路，研究CXCR4及信号通路在胞外游离泛素对放射损伤影响中的机理；采用正常和肠上皮细胞CXCR4基因敲除小鼠，研究外源性游离泛素对CXCR4功能正常/缺失小鼠的放射防护作用；采用两种小鼠和它们的皮肤、肺、肠组织原代细胞，研究游离泛素对这些组织放射损伤的影响，验证CXCR4的作用机理。本项目旨在阐明细胞外游离泛素通过CXCR4跨膜受体及通路在放射损伤防护中的作用机理。

During cancer radiotherapy and nuclear accidents, ionizing radiation is likely to cause injuries to normal tissues. Our previous results showed that: (1) the levels of extracellular free ubiquitin are closely related to radiation-induced injury tissue radiosensitivity. and (2) free ubiquitin has the funcation to lighten radiation-induced injury. CXCR4, a transmembrane signal receptor, has the ability to transmit extracellular signal to intracellular. In this project, we will investigate the mechanism that how free ubiquitin exerts its radio-protective effect via CXCR4 transmembrane receptor. We will analysize skin, intestinal and lung tissues and derived cells, which have important biological functions but different radiosensitivities. The radio-protective mechanism of free ubiquitin will be explored by changing the levels of free ubiquitin and CXCR4 inhibition. The CXCR4 signaling pathway will be studied by chemical inhibitor or siRNAs to illustrate its role in mediating free ubiquitin-induced intracellular signal transduction. In addition, C57 wild-type and intestinal epithelia CXCR4 knock-out mice will be used to investigate the radio-protective role of free ubiquitin in vivo. The survival experiment and primary cells from skin, intestinal and lung tissues will be used to compare the radio-protective role of free ubiquitin in different tissues, confirming the role of CXCR4 pathway. This project aims to illustrate the radio-protective role and mechanism of free ubiquitin against ionizing radiation via CXCR4 signaling pathway.