摘要
目的通过研究外周血单个核细胞(PBMC)中炎症相关基因的变化,探讨维生素D对炎症性肠病(IBD)发病的作用机制。方法在GEO数据库中的GSE50012下载24个样本量,分为服用维生素D患者组和未服用维生素D患者组,每组12例,寻找2组患者PBMC中mRNA的差异性表达,同时对差异性表达的基因进行GO/KEGG和GSEA富集分析,寻找可能参与的通路或分子功能,对差异基因进行分子互作网络分析,寻找关键基因Hub。收集处于活动期的128例溃疡性结肠炎(UC)和62例克罗恩病(CD)患者,通过是否服用维生素D分为4组,分别测定每组PBMC中的候选关键基因表达,评价维生素D对IBD的作用。结果GEO数据库筛选出差异表达基因(DEGs)共计128个,其中高表达53个,低表达75个,GO分析结果显示DEGs主要参与细胞因子活性、趋化因子与受体结合、调节炎症反应、参与免疫效应过程、介导淋巴细胞免疫等过程,KEGG分析得出细胞因子-细胞因子受体相互作用、IBD、IgA介导的肠道免疫网络等信号通路;GSEA分析结果表明差异性表达的分子主要参与了维生素D受体途径、KEGG趋化因子信号通路等,蛋白互作网络分析筛选出IL-6、MMP9、CXCL9、CXCL10、TREM1、IL1R2、C1QB这7个关键基因,加用维生素D后HLA-DMA、HLA-DMB、IL-6、MMP9、CXCL9、CXCL10呈现低表达,而NOD2呈现高表达。结论维生素D通过影响PBMC炎症相关基因进而抑制炎症、调节免疫功能,可能对IBD起到保护作用,为后期IBD的基础与临床研究提供思路。
Objective To investigate the role of Vitamin D in the pathogenesis of inflammatory bowel disease(IBD)by studying the changes of inflammation related genes in peripheral blood mononuclear cells(PBMC).Methods 24 sample sizes were downloaded from GSE50012 in the GEO database,and they were divided into two groups:patients taking Vitamin D and patients not taking Vitamin D,with 12 patients in each group.Find out the differential expression of mRNA in PBMC of two groups of patients.At the same time,we conducted GO/KEGG and GSEA enrichment analysis on the differentially expressed genes,searched for possible pathways or molecular functions,conducted molecular interaction network analysis on the differential genes,and searched for key genes(Hub genes).A total of 128 patients with ulcerative colitis(UC)and 62 patients with Crohn′s disease(CD)in the outpatient department of our hospital were collected and divided into 4 groups by whether to take Vitamin D or not.Candidate key gene expression in PBMC in each group was measured to evaluate the effect of Vitamin D on inflammatory bowel disease.Results The GEO database screened a total of 128 differential expression genes(DEGs),of which 53 were highly expressed and 75 were low expressed.GO analysis showed that DEGs were mainly involved in cytokine activity,chemokine receptor binding,regulating inflammatory reactions,participating in immune response processes,mediating lymphocyte immunity,and other processes.KEGG analysis showed that cytokine receptor interaction,inflammatory bowel disease IgA mediated signaling pathways such as intestinal immune networks;GSEA analysis showed that the differentially expressed molecules were mainly involved in the Vitamin D receptor pathway and the KEGG chemokine signaling pathway.Protein interaction network analysis screened seven key genes,IL-6,MMP9,CXCL9,CXCL10,TREM1,IL1R2,and C1QB.After adding Vitamin D,HLA-DMA,HLA-DMB,IL-6,MMP9,CXCL9,and CXCL10 showed low expression,while NOD2 showed high expression.Conclusion Vitamin D may play a protective role in IBD by influencing PBMC inflammation related genes,thereby inhibiting inflammation and regulating immune function,providing ideas for the basic and clinical research of late IBD.
作者
徐艳秋
陈卫刚
Xu Yanqiu;Chen Weigang(Dept of Gastroenterology,The First Affiliated Hospital of Shihezi University Medical College,Shihezi 832000)
出处
《安徽医科大学学报》
CAS
北大核心
2023年第6期941-947,共7页
Acta Universitatis Medicinalis Anhui
基金
国家重点研发计划课题(编号:2016YFC1303601)。
关键词
炎症性肠病
单个核细胞
维生素D
溃疡性结肠炎
克罗恩病
inflammatory bowel disease
mononuclear cells
Vitamin D
ulcerative colitis
Crohn′s disease
