Chen Lijian, Peng Yuming, Ji Chunyi, Yuan Miaoxian, Yin Qiang
Department of General Surgery, Hunan Children's Hospital, Changsha 410007, PR China.
Saudi J Biol Sci. 2021 Mar;28(3):1569-1575. doi: 10.1016/j.sjbs.2020.12.050. Epub 2021 Jan 13.
Tacrolimus is a powerful immunosuppressant and has been widely used in organ transplantation. In order to further explore the role of tacrolimus in liver transplantation, we conducted network pharmacology analysis.
GSE100155 was obtained from the GEO database, and the DEGs of liver transplantation were analyzed. The 2D structure of tacrolimus was obtained from the National Library of Medicine, and the pharmacophore model of tacrolimus was predicted using the online tool pharmmapper. Then a network of tacrolimus and target genes was constructed through network pharmacology, and visualization and GO enrichment analysis was performed through Cytoscape. In addition, we also analyzed the correlation between key genes and immune infiltrating cells. The data of GSE84908 was used to verify the changes of key gene expression levels after tacrolimus treatment.
The results of network pharmacological analysis showed that tacrolimus had 43 target genes, and the GO enrichment results showed many potential functions. Further analysis found that there were 5 key target genes in DEGs, and these 5 genes were significantly down-regulated in liver transplant patients. Another important finding was that 5 genes were significantly related to some immune infiltrating cells. The results of the GSE84908 data analysis showed that after tacrolimus treatment, the expression of was significantly increased ( = 0.015).
Tacrolimus may inhibit the human immune response by affecting the expression of in liver transplant patients.
他克莫司是一种强效免疫抑制剂,已广泛应用于器官移植。为了进一步探讨他克莫司在肝移植中的作用,我们进行了网络药理学分析。
从基因表达综合数据库(GEO数据库)获取GSE100155数据,并分析肝移植的差异表达基因(DEGs)。他克莫司的二维结构从美国国立医学图书馆获取,并使用在线工具PharmMapper预测他克莫司的药效团模型。然后通过网络药理学构建他克莫司与靶基因的网络,并通过Cytoscape进行可视化和基因本体(GO)富集分析。此外,我们还分析了关键基因与免疫浸润细胞之间的相关性。使用GSE84908数据验证他克莫司治疗后关键基因表达水平的变化。
网络药理学分析结果显示他克莫司有43个靶基因,GO富集结果显示了许多潜在功能。进一步分析发现差异表达基因中有5个关键靶基因,这5个基因在肝移植患者中显著下调。另一个重要发现是5个基因与一些免疫浸润细胞显著相关。GSE84908数据分析结果显示,他克莫司治疗后,(此处原文缺失具体基因名)的表达显著增加(P = 0.015)。
他克莫司可能通过影响肝移植患者中(此处原文缺失具体基因名)的表达来抑制人体免疫反应。