Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Laboratory of Experimental Pharmacology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy.
Front Immunol. 2021 Aug 24;12:709173. doi: 10.3389/fimmu.2021.709173. eCollection 2021.
Although the exact pathophysiology of MS has not been identified, mitochondrial stress can be one of the culprits in MS development. Herein, we have applied microarray analysis, single-cell sequencing analysis, and study to elucidate the role of mitochondrial stress in PBMCs of MS patients.
For this purpose, we analyzed the GSE21942 and GSE138266 datasets to identify the DEGs and hub genes in the PBMCS of MS patients and describe the expression of shared genes in the different immune cells. The GO pathway analysis of DEGs and turquoise module genes were conducted to shed light on their biological significance. To validate the obtained results, the gene expression of , as the most remarkable DEG in the PBMCS of affected patients, was measured in the PBMCS of healthy donors, treatment-naïve MS patients, and MS patients treated with GA, fingolimod, DMF, and IFNβ-1α.
Based on WGCNA and DEGs analysis, , and are the identified common genes in the PMBCS. Using single-cell sequencing analysis on PBMCS, we have characterized various cell populations in MS and illustrated the common gene expression on the different immune cells. Furthermore, GO pathway analysis of DEGs, and turquoise module genes have indicated that these genes are involved in immune responses, myeloid cell activation, leukocyte activation, oxygen carrier activity, and replication fork processing bicarbonate transport pathways. Our investigation has shown that expression in the treatment-naïve RRMS patients is significantly increased compared to healthy donors. Of interest, immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α have significantly decreased expression.
is one of the remarkably up-regulated genes in the PBMCS of MS patients. is substantially up-regulated in treatment-naïve MS patients, and immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α can remarkably down-regulate expression. Based on the currently available evidence, the cytoprotective nature of HBD against oxidative stress can be the underlying reason for HBD up-regulation in MS. Nevertheless, further investigations are needed to shed light on the molecular mechanisms of HBD in the oxidative stress of MS patients.
尽管多发性硬化症的确切病理生理学尚未确定，但线粒体应激可能是多发性硬化症发展的罪魁祸首之一。在此，我们应用了微阵列分析、单细胞测序分析和研究，以阐明线粒体应激在多发性硬化症患者 PBMCs 中的作用。
为此，我们分析了 GSE21942 和 GSE138266 数据集，以鉴定多发性硬化症患者 PBMCs 中的差异表达基因和枢纽基因，并描述不同免疫细胞中共享基因的表达。对差异表达基因和绿松石模块基因进行 GO 通路分析，以揭示其生物学意义。为了验证获得的结果，我们测量了健康供体、未经治疗的多发性硬化症患者和接受 GA、芬戈莫德、DMF 和 IFNβ-1α 治疗的多发性硬化症患者 PBMCs 中最显著差异表达基因的基因表达。
基于 WGCNA 和差异表达基因分析， 、 和 是 PBMCs 中鉴定的共同基因。使用 PBMCs 的单细胞测序分析，我们对多发性硬化症中的各种细胞群进行了特征描述，并说明了不同免疫细胞上的共同基因表达。此外，差异表达基因和绿松石模块基因的 GO 通路分析表明，这些基因参与免疫反应、髓样细胞激活、白细胞激活、氧载体活性和复制叉加工碳酸氢盐转运途径。我们的研究表明，未经治疗的 RRMS 患者的 表达明显高于健康供体。有趣的是，芬戈莫德、DMF 和 IFNβ-1α 的免疫调节治疗显著降低了 表达。
是多发性硬化症患者 PBMCs 中显著上调的基因之一。未经治疗的多发性硬化症患者中 显著上调，芬戈莫德、DMF 和 IFNβ-1α 的免疫调节治疗可显著下调 表达。根据目前的证据，HBD 对氧化应激的细胞保护特性可能是 HBD 在多发性硬化症中上调的原因。然而，需要进一步的研究来阐明 HBD 在多发性硬化症患者氧化应激中的分子机制。
