Soad Ghabeshi, Ali Najafi, Batol Zamani, Mozhdeh Soltani, Amanuel Godana Arero, Shim Izadi, Ahmad Piroozmand
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引用次数: 1
摘要
背景:大量证据支持SLE可能与细胞凋亡和EBV感染有关。目的:本研究的目的是鉴定EBV感染SLE患者的转录特征,以调查分子凋亡信号通路。方法:从GEO获取健康对照和SLE患者的PBMCs基因表达谱。使用DAVID、KEGG进行功能注释和信号通路富集。为了验证生物信息学分析中部分基因表达变化的有效性,我们对28例SLE患者和18例对照组的pbmc进行了Real time PCR检测。结果:所有患者外周血单核细胞的平均病毒载量为6013±390.1拷贝/μg DNA。QRT-PCR结果显示,4个候选基因中logFC变化最大的DUSP1和LAMP3基因的表达量较对照显著升高。LMP2作为参与细胞凋亡信号通路的病毒潜伏期基因,在EBV病毒载量的SLE患者和部分对照组中表达一致。结论:本研究提示一些细胞基因可能通过凋亡信号通路在SLE发病中起重要作用。此外,EBV感染作为SLE的环境危险因素可能影响细胞凋亡功能障碍。
Evaluation of molecular apoptosis signaling pathways and its correlation with EBV viral load in SLE patients using systems biology approach.
Background: Considerable evidence supports that SLE could be related to apoptotic cells and EBV infection.
Objective: The aim of this study was to identify the transcriptional signature of EBV infection in SLE patients for survey of the molecular apoptosis signaling pathways.
Methods: The PBMCs gene expression profiles of healthy control and SLE patients were obtained from GEO. Functional annotation and signaling pathway enrichment were carried out using DAVID, KEGG. To validate bioinformatics analysis the changes in genes expression of some of obtained genes, Real time PCR was performed on PBMCs from 28 SLE patients and 18 controls.
Results: We found that mean viral load was 6013 ± 390.1 copy/μg DNA from PBMCs in all patients. QRT-PCR results showed that the expression of the DUSP1 and LAMP3 genes which had most changes in the logFC among 4 candidate genes, increased significantly in comparison with control. The consistent expression of LMP2 as viral latency gene involve in apoptosis signaling pathways was detected in SLE patients with EBV viral load and some controls.
Conclusions: The study indicated that some cellular genes may have an important role in pathogenesis of SLE through apoptosis signaling pathways. Beside, EBV infection as an environmental risk factor for SLE may affect the dysfunction of apoptosis.
期刊介绍:
Human Antibodies is an international journal designed to bring together all aspects of human hybridomas and antibody technology under a single, cohesive theme. This includes fundamental research, applied science and clinical applications. Emphasis in the published articles is on antisera, monoclonal antibodies, fusion partners, EBV transformation, transfections, in vitro immunization, defined antigens, tissue reactivity, scale-up production, chimeric antibodies, autoimmunity, natural antibodies/immune response, anti-idiotypes, and hybridomas secreting interesting growth factors. Immunoregulatory molecules, including T cell hybridomas, will also be featured.