基于整合生物信息学分析的多发性硬化症妊娠期间的基因表达。

Gene expression in multiple sclerosis during pregnancy based on integrated bioinformatics analysis.

机构信息

High Specialty Medical Unit, Pediatric Hospital, Western National Medical Center of the Mexican Institute of Social Security, Guadalajara 44340, Mexico; Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico.

Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico; Neurosciences Division, Western Biomedical Research Center (IMSS), Guadalajara 44340, Mexico.

出版信息

Mult Scler Relat Disord. 2024 Feb;82:105373. doi: 10.1016/j.msard.2023.105373. Epub 2023 Dec 14.

DOI:10.1016/j.msard.2023.105373

PMID:38154347

Abstract

BACKGROUND

The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS.

METHODS

Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS.

RESULTS

We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P).

CONCLUSION

This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.

摘要

背景

多发性硬化症（MS）患者在怀孕期间疾病活动的调节是一个有用的模型，它可以深入了解中枢疾病机制，并有助于治疗。因此，本研究的目的是从妊娠 MS 患者中鉴定差异表达基因，进行生物功能途径富集分析和蛋白质-蛋白质相互作用。

方法

从基因表达综合数据库（GEO）数据库中获取转录组数据。我们选择了微阵列数据集 GSE17449。基因表达数据集包含四个不同组的单核细胞数据，包括 7 名健康女性（H）、4 名健康孕妇（HP）、8 名多发性硬化症女性（WMS）和 9 名多发性硬化症妊娠 9 个月的女性（PMS）。使用 GSEA 软件进行富集分析，使用 REACTOME 数据库进行生物途径分析。使用 STRING 绘制蛋白质-蛋白质相互作用（PPI）网络。使用 KEGG 和 WIKIPATHWAYS 数据库识别差异表达基因与不同信号通路的连接。

结果

我们在妊娠 MS 患者中鉴定出 42 个差异表达基因。显著途径包括 IL-10 信号通路、ErbB2 激活、血红蛋白复合物（HBD、HBB、HBA1、AHSP 和 HBA2）、IL-17 信号通路（LCN2 和 MMP9）、抗原加工和呈递、Th17 细胞分化（HLA-DQA1）、Rap1 信号通路（ID1）、NOD-样受体信号通路（CAMP 和 DEFA4）、PD-L1 信号、干扰素γ信号（MMP9 和 ARG1）、嗜中性粒细胞脱颗粒（CAMP、DEFA4、ELANE、CEACAM8、S100P、CHI3L1、AZU1、OLFM4、CRISP3、LTF、ARG1、PGLYRP1 和 TCN1）。在 WIKIPATHWAYS 集中，发现了维生素 B12 代谢（TCN1、HBB 和 HBA2）和 IL-18 信号通路（S100P）的意义。