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分析磁悬浮模拟微重力环境对巨噬细胞中Arp2/3复合体通路的影响。

Analysis of the effects of magnetic levitation to simulate microgravity environment on the Arp2/3 complex pathway in macrophage.

作者信息

Wang Sufang, Zhang Nu, Di Jianglei, Zhao Wenjuan, Shi Guolin, Xie Ruiheng, Hu Bohan, Yang Hui

机构信息

School of Life Sciences, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China.

Center of Special Environmental Biomechanics & Biomedical Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China.

出版信息

J Biol Phys. 2021 Sep;47(3):323-335. doi: 10.1007/s10867-021-09581-w. Epub 2021 Sep 17.

Abstract

With dwindling natural resources on earth, current and future generations will need to explore space to new planets that will require travel under no or varying gravity conditions. Hence, long-term space missions and anticipated impacts on human biology such as changes in immune function are of growing research interest. Here, we reported new findings on mechanisms of immune response to microgravity with a focus on macrophage as a cellular model. We employed a superconducting magnet to generate a simulated microgravity environment and evaluated the effects of simulated microgravity on RAW 264.7 mouse macrophage cell line in three time frames: 8, 24, and 48 h. As study endpoints, we measured cell viability, phagocytosis, and used next-generation sequencing to explore its changing mechanism. Macrophage cell viability and phagocytosis both showed a marked decrease under microgravity. The differentially expressed genes (DEG) were identified in two ways: (1) gravity-dependent DEG, compared μg samples and 1 g samples at each time point; (2) time-dependent DEG, compared time-point samples within the same gravitational field. Through transcriptome analysis and confirmed by molecular biological verification, our findings firstly suggest that microgravity might affect macrophage phagocytosis by targeting Arp2/3 complex involved cytoskeleton synthesis and causing macrophage immune dysfunction. Our findings contribute to an emerging body of scholarship on biological effects of space travel.

摘要

随着地球上自然资源的日益减少,当代人和后代人将需要探索太空,前往新的行星,而这将需要在零重力或变化的重力条件下进行旅行。因此,长期太空任务以及对人类生物学的预期影响,如免疫功能的变化,正成为越来越受关注的研究领域。在此,我们报告了关于微重力免疫反应机制的新发现,重点是以巨噬细胞作为细胞模型。我们使用超导磁体来产生模拟微重力环境,并在三个时间点(8小时、24小时和48小时)评估模拟微重力对RAW 264.7小鼠巨噬细胞系的影响。作为研究终点,我们测量了细胞活力、吞噬作用,并使用下一代测序技术来探索其变化机制。在微重力条件下,巨噬细胞的细胞活力和吞噬作用均显著下降。差异表达基因(DEG)通过两种方式确定:(1)重力依赖性DEG,比较每个时间点的μg样本和1g样本;(2)时间依赖性DEG,比较同一重力场中的时间点样本。通过转录组分析并经分子生物学验证,我们的研究结果首次表明,微重力可能通过靶向参与细胞骨架合成的Arp2/3复合体并导致巨噬细胞免疫功能障碍,从而影响巨噬细胞的吞噬作用。我们的研究结果为有关太空旅行生物学效应的新兴学术研究做出了贡献。

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