Chai Shaobin, Guo Song, Yang Jiaqi, Lu Shengyu, Yue Yuan, Li Hao, Sun Peiming, Zhang Tao, Xu Binxin, Sun Hongwei, Si Shaoyan, Zhou Jinlian, Yang Jianwu, Yang Heming, Li Zhengpeng, Cui Yan
Medical School of Chinese PLA Beijing 100853, China.
Department of General Surgery, Strategic Support Force Medical Center Beijing 100101, China.
Am J Transl Res. 2021 Aug 15;13(8):9195-9207. eCollection 2021.
Astronauts suffer from inflammatory changes induced by microgravity during space flight. Microgravity can significantly affect the inflammatory response of various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and digestive system. The aim of this research was to identify the key genes and pathways of gastric mucosa affected by microgravity. Human gastric mucosal epithelial GES-1 cells were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The gene expression profiles of GES-1 cells were obtained using Illumina sequencing platform and differentially expressed genes were identified by DESeq2 software, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Subsequently, a protein-protein interaction (PPI) network was constructed. Compared with a normal gravity (NG) group, a total of 943 DEGs, including 192 downregulated genes and 751 upregulated genes, were identified. These DEGs were associated with findings that included response to interleukin-1, positive regulation of inflammatory response, and positive regulation of neuroinflammatory response. Furthermore, these DEGs were mainly enriched in herpes simplex virus 1 infection, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathway. Thus, 21 hub genes were identified from PPI network, including IL6, IL1B, ITGAM, CXCL8, ITGAX, CCL5, SERPINA1, APOE, CSF1R, VWF, GBP1, APOB, CYBB, HLA-DRB1, CD68, FGG, FGA, OASL, NOD2, OAS2 and FCGR2A. These findings suggested that simulated microgravity upregulated inflammation-related genes and pathways of GES-1 cells, which may play important roles in the response to microgravity and provide useful information for preventing mucosal damage in astronauts. In conclusion, this study revealed the key genes and pathways associated with simulated microgravity and indicated that simulated microgravity induced an inflammatory response in gastric mucosal epithelial cells.
宇航员在太空飞行期间会遭受微重力诱导的炎症变化。微重力会显著影响人体各种细胞类型和多个系统的炎症反应,如心血管系统、骨骼肌系统和消化系统。本研究的目的是确定受微重力影响的胃黏膜关键基因和信号通路。将人胃黏膜上皮GES-1细胞培养在旋转细胞培养系统(RCCS)生物反应器中以模拟微重力。使用Illumina测序平台获得GES-1细胞的基因表达谱,并通过DESeq2软件鉴定差异表达基因,然后进行基因本体(GO)和京都基因与基因组百科全书(KEGG)信号通路分析。随后,构建了蛋白质-蛋白质相互作用(PPI)网络。与正常重力(NG)组相比,共鉴定出943个差异表达基因,包括192个下调基因和751个上调基因。这些差异表达基因与包括对白介素-1的反应、炎症反应的正调控和神经炎症反应的正调控等结果相关。此外,这些差异表达基因主要富集在单纯疱疹病毒1感染、细胞因子-细胞因子受体相互作用和NOD样受体信号通路中。因此,从PPI网络中鉴定出21个核心基因,包括IL6、IL1B、ITGAM、CXCL8、ITGAX、CCL5、SERPINA1、APOE、CSF1R、VWF、GBP1、APOB、CYBB、HLA-DRB1、CD68、FGG、FGA、OASL、NOD2、OAS2和FCGR2A。这些发现表明,模拟微重力上调了GES-1细胞的炎症相关基因和信号通路,这可能在对微重力的反应中起重要作用,并为预防宇航员的黏膜损伤提供有用信息。总之,本研究揭示了与模拟微重力相关的关键基因和信号通路,并表明模拟微重力在胃黏膜上皮细胞中诱导了炎症反应。