Xu Guangyu, Feng Yanbo, Li Han, Chen Cong, Li He, Wang Chunmei, Chen Jianguang, Sun Jinghui
College of Pharmacy, Beihua University, Jilin, China.
Front Pharmacol. 2021 Dec 20;12:785353. doi: 10.3389/fphar.2021.785353. eCollection 2021.
The molecular mechanism of the regulatory effed of schizandrol A (SA) on the immune function of cyclophosphamide-induced immunosuppressive mice was explored in this study. On the basis of 1619 differentially expressed genes related to the regulatory effect of SA on the immune function of mice screened in our previous study, transcription factors and their corresponding target genes were screened in the Transcriptional Regulatory Element Database (TRED), and a transcription factor target gene regulatory network was constructed. The key nodes of the network were statistically analyzed to clarify the role of transcription factors in the regulatory network. The correlation of network genes with diseases was analyzed with an online annotation tool through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, the key factors related to the regulatory effect of SA on the immune function of mice were screened and verified by animal experiments and the detection of related protein expression by western blot analysis. The results showed that SA could alleviate the immunosuppression induced by cyclophosphamide in mice and regulate the protein expression of Jun, Trp53, and Creb1 in the spleen tissue of mice, together with the transcription factors Atf4 and E2f2. SA may thus play a role in the alleviation of some immunity-related diseases (such as cancer) by regulating the immune function of mice through multiple genes and their transcription factors.
本研究探讨了五味子醇甲(SA)对环磷酰胺诱导的免疫抑制小鼠免疫功能的调节作用的分子机制。基于我们之前研究中筛选出的1619个与SA对小鼠免疫功能调节作用相关的差异表达基因,在转录调控元件数据库(TRED)中筛选转录因子及其相应的靶基因,并构建转录因子靶基因调控网络。对网络的关键节点进行统计分析,以阐明转录因子在调控网络中的作用。通过注释、可视化和综合发现数据库(DAVID),利用在线注释工具分析网络基因与疾病的相关性。最后,通过动物实验和蛋白质免疫印迹分析检测相关蛋白表达,筛选并验证了与SA对小鼠免疫功能调节作用相关的关键因子。结果表明,SA可减轻环磷酰胺诱导的小鼠免疫抑制,并调节小鼠脾脏组织中Jun、Trp53和Creb1的蛋白表达,以及转录因子Atf4和E2f2。因此,SA可能通过多个基因及其转录因子调节小鼠的免疫功能,在缓解某些免疫相关疾病(如癌症)中发挥作用。