NLRP3通过减弱cGAS-STING信号通路保护小鼠免受辐射诱导的结肠和皮肤损伤。
NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling.
作者信息
Wu Tiancong, Gao Jianhua, Liu Wen, Cui Jian, Yang Miaofang, Guo Wenjie, Wang Fang-Yu
机构信息
Department of Gastroenterology and Hepatology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China; Jinling Hospital, Department of Radiation Oncology, Nanjing University, School Medicine, Nanjing 210002, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China.
出版信息
Toxicol Appl Pharmacol. 2021 May 1;418:115495. doi: 10.1016/j.taap.2021.115495. Epub 2021 Mar 17.
In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-β levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-β in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.
在本研究中，在体内和体外探讨了NLRP3对辐射诱导的组织损伤（包括小鼠结肠和皮肤损伤）的影响及其可能机制。通过定时暴露于X射线对小鼠进行全腹辐射，累积剂量为14 Gy。生存率表明，NLRP3缺乏会增加小鼠的死亡率。此外，通过苏木精-伊红（H&E）染色和屏障功能分析评估，NLRP3缺乏会显著加重结肠损伤。结肠组织中p-TBK1和p-IRF3的磷酸化增强以及血清中IFN-β水平升高表明cGAS-STING信号通路过度激活。此外，在体外NLRP3基因敲除后，骨髓来源的巨噬细胞（BMDMs）中辐射诱导的p-TBK1、p-IRF3和IFN-β表达增加。因此，我们的研究结果表明，NLRP3可能通过减弱cGAS-STING信号通路来保护小鼠免受辐射诱导的组织损伤。
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