通过系统生物学破译皮肤利什曼病、发病机制和药物再利用的分子机制。

Q2 Biochemistry, Genetics and Molecular Biology Iranian Biomedical Journal Pub Date : 2024-07-01 DOI:10.61186/ibj.4177
Fatemeh Saberi, Zeinab Dehghan, Zahra Taheri, Tayyebeh Pilehchi, Zali Hakimeh
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引用次数: 0

摘要

背景:皮肤利什曼病是由利什曼病属细胞内病原体引起的重大健康问题。皮肤利什曼病导致形态各异的皮肤损伤,从结节到斑块和溃疡不等,根据污染寄生虫的类型,这些损伤会持续不断地恢复。目前还没有有效的治疗方法来减轻感染 CL 患者的皮肤损伤。本研究旨在制定治疗 CL 患者皮损的策略:我们从 GEO 数据库中检索了 CL 患者皮损和正常皮肤的转录组数据。使用 STRING 数据库和 Cytoscape v3.10.1 软件构建了 PPIN。通过拓扑网络分析和聚类检测确定了关键基因。最后,确定了关键基因的基因本体和再利用药物:结果:CD8A、IFNG、IL-6、PTPRC、CCR7、TLR2、GSTA5、CYBB、IL-12RB2、ITGB2、FCGR3A、CTLA4和IFNG被确定为PPIN和子网络中的关键基因。富集分析显示,T细胞受体信号转导、TLR信号转导、细胞因子-细胞因子受体相互作用、移植物抗宿主疾病、利什曼病、趋化因子信号转导、原发性免疫缺陷和Th17细胞分化是与关键基因相关的主要通路。药物再利用的结果表明,环孢素、利妥昔单抗、英夫利昔单抗、blinatumomab和甲泼尼龙是治疗CL的候选药物:结论:在用现有的实验数据验证了我们的模型后,我们发现在前瞻性研究中,关键分子和候选药物在治疗利什曼原虫引起的皮肤病变中起着至关重要的作用。
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Deciphering Molecular Mechanisms of Cutaneous Leishmaniasis, Pathogenesis and Drug Repurposing through Systems Biology

Background: Cutaneous leishmaniasis (CL) is a major health problem caused by an intracellular pathogen of the genus Leishmania. CL results in morphologically distinct skin injuries, ranging from nodules to plaques and ulcers, which persist as a recuperating incessant injury depending on the type of contaminating parasite. There is still no effective treatment to reduce the skin lesions in patients infected with CL. The aim of this study was to develop strategies to treat skin lesions in CL patients.

Methods: We retrieved the transcriptomic data of skin lesions from patients with CL and normal skin from the gene Expression Omnibus (GEO) database. The protein-protein interaction network (PPIN) was constructed using the STRING database and Cytoscape v3.10.1 software. Critical genes were identified by topological network analysis and cluster detection. Finally, gene ontology and repurposing drugs for critical genes were determined.

Results: CD8A, IFNG, IL-6, PTPRC, CCR7, TLR2, GSTA5, CYBB, IL-12RB2, ITGB2, FCGR3A, CTLA4, and IFNG were identified as the critical genes in PPIN and subnetworks. Enrichment analysis revealed that T-cell receptor signaling, toll-like receptor signaling, cytokine-cytokine receptor interaction, graft-versus-host disease, leishmaniasis, chemokine signaling, primary immunodeficiency, and Th17 cell differentiation were the major pathways associated with critical genes. The drug repurposing results identified cyclosporine, rituximab, infliximab, blinatumomab, and methylprednisolone as candidates for treatment of CL.

Conclusion: After validating our model with available experimental data, we found that critical molecules and drug candidates play a crucial role in the treatment of skin lesions caused by Leishmania in prospective studies.

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来源期刊
Iranian Biomedical Journal
Iranian Biomedical Journal Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
3.20
自引率
0.00%
发文量
42
审稿时长
8 weeks
期刊最新文献
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