摘要
目的 探讨抑郁症加重克罗恩病的关键基因和机制.方法 于2023年3月分析公共卫生基因组学知识库及基因表达综合数据库识别克罗恩病和抑郁症之间重叠的差异表达基因,通过Metascape、STRING和Cytoscape、蛋白互作网络分析筛选出关键基因,利用基因表达综合数据库探讨关键基因与克罗恩病内镜下严重指数、肠道微绒毛长度等临床病理的关联性.结果 共有137个克罗恩病和抑郁症的重叠差异表达基因,进一步筛选出了 25 个关键基因,其中,基因 CREB1、FKBP5、MAPT、NTSR1、OXTR、PROK2、POMC、HTR2B、PPARGC1A与多个临床参数显著关联,PROK2和PROK2相关基因的功能主要富集在中性粒细胞和粒细胞的迁移、中性粒细胞和粒细胞的趋化等方面.结论 25个关键基因,特别是CREB1、FKBP5、MAPT、NTSR1、OXTR、PROK2、POMC、HTR2B和PPARGC1A,可能与抑郁症加重克罗恩病有关.其中PROK2可能通过调节免疫细胞(中性粒细胞和CD8+T细胞)的浸润发挥作用.
Abstract
Objective To explore key genes and mechanisms of depression aggravating Crohn disease.Methods In March 2023,the Public Health Genomics and Precision Health Knowledge Base and Gene Expression Omnibus database were used to identify the overlapping differentially expressed genes between Crohn disease and depression and the key genes were screened by Metascape,STRING,Cytoscape,and protein interaction network analysis.The Gene Expression Omnibus database was used to analyze the correlations between key genes and clinical pathologies such as Crohn Disease Endoscopic Index of Severity and intestinal microvilli length.Results There were 137 overlapping differentially expressed genes between Crohn disease and depression,and 25 key genes were further screened out.Among them,CREB1,FKBP5,MAPT,NTSR1,OXTR,PROK2,POMC,HTR2B,and PPARGC1A genes were significantly correlated with multiple clinical parameters.The functions of PROK2 and PROK2-related genes were mainly enriched in neutrophil and granulocyte migration,neutrophil and granulocyte chemotaxis,etc.Conclusions There are 25 key genes,especially CREB1,FKBP5,MAPT,NTSR1,OXTR,PROK2,POMC,HTR2B,and PPARGC1A,that possibly contribute to the establishment and deterioration of Crohn disease caused by depressive disorder.Among these genes,PROK2 showes the possibility of regulating immune cell(neutrophils and CD8+T cells)infiltration.
基金项目
四川大学华西医院学科卓越发展1.3.5工程项目(ZYJC21044)
维普
万方数据