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循环miR-342-3p的调控减轻辐射诱导的免疫系统损伤。

Regulation of Circulating miR-342-3p Alleviates the Radiation-Induced Immune System Injury.

作者信息

Wei Wenjun, Bai Hao, Zhang Tianyi, Cai Shufan, Zhou Yumeng, Liu Min, Zhang Yanan, Chen Yaxiong, Hua Junrui, He Jinpeng, Ding Nan, Miao GuoYing, Wang Jufang

机构信息

Biomedical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.

出版信息

Radiat Res. 2023 Dec 1;200(6):556-568. doi: 10.1667/RADE-23-00125.1.

Abstract

Ionizing radiation in space, radiation devices or nuclear disasters are major threats to human health and public security. Expanding countermeasures for dealing with accidental or occupational radiation exposure is crucial for the protection of radiation injuries. Circulating microRNAs (miRNAs) have emerged as promising radiation biomarkers in recent years. However, the origin, distribution and functions of radiosensitive circulating miRNAs remain unclear, which obstructs their clinical applications in the future. In this study, we found that mmu-miR-342-3p (miR-342) in mouse serum presents a stable and significant decrease after X-ray total-body irradiation (TBI). Focusing on this miRNA, we investigated the influences of circulating miR-342 on the radiation-induced injury. Through tail vein injection of Cy5-labeled synthetic miR-342, we found the exogenous miR-342-Cy5 was mainly enriched in metabolic and immune organs. Besides, the bioinformatic analysis predicted that miR-342 might involve in immune-related processes or pathways. Further, mice were tail vein injected with synthetic miR-342 mimetics (Ago-miR-342) after irradiation to upregulate the level of miR-342 in circulating blood. The results showed that the upregulation of circulating miR-342 alleviated the radiation-induced depletion of CD3+CD4+ T lymphocytes and influenced the levels of IL-2 and IL-6 in irradiated mice. Moreover, the injection of Ago-miR-342 improved the survival rates of mice with acute radiation injury. Our findings demonstrate that upregulation of circulating miR-342 alleviates the radiation-induced immune system injury, which provides us new insights into the functions of circulating miRNAs and the prospect as the targets for mitigation of radiation injuries.

摘要

太空电离辐射、辐射装置或核灾难对人类健康和公共安全构成重大威胁。扩大应对意外或职业性辐射暴露的对策对于预防辐射损伤至关重要。近年来,循环微小核糖核酸(miRNA)已成为很有前景的辐射生物标志物。然而,放射敏感的循环miRNA的来源、分布和功能仍不清楚,这阻碍了它们未来的临床应用。在本研究中,我们发现小鼠血清中的mmu-miR-342-3p(miR-342)在X射线全身照射(TBI)后呈现稳定且显著的下降。针对这种miRNA,我们研究了循环miR-342对辐射诱导损伤的影响。通过尾静脉注射Cy5标记的合成miR-342,我们发现外源性miR-342-Cy5主要富集于代谢和免疫器官。此外,生物信息学分析预测miR-342可能参与免疫相关过程或途径。进一步地,在照射后给小鼠尾静脉注射合成的miR-342模拟物(Ago-miR-342)以上调循环血液中miR-342的水平。结果显示,循环miR-342的上调减轻了辐射诱导的CD3+CD4+ T淋巴细胞耗竭,并影响了受照射小鼠中白细胞介素-2和白细胞介素-6的水平。此外,注射Ago-miR-342提高了急性辐射损伤小鼠的存活率。我们的研究结果表明,循环miR-342的上调减轻了辐射诱导的免疫系统损伤,这为我们提供了关于循环miRNA功能以及作为减轻辐射损伤靶点的前景的新见解。

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