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通过综合生物信息学分析鉴定硕大利什曼原虫感染中的基因表达谱。

Identification of gene expression profiles in Leishmania major infection by integrated bioinformatics analyses.

作者信息

Ulusan Özlem, Mert Ufuk, Sadıqova Aygül, Öztürk Sercan, Caner Ayse

机构信息

Department of Parasitology, Ege University Medical School, Izmir, Turkey.

Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey.

出版信息

Acta Trop. 2020 Aug;208:105517. doi: 10.1016/j.actatropica.2020.105517. Epub 2020 Apr 28.

Abstract

Gene expression profiling in mouse models of leishmaniasis has given useful information to understand the molecular pathways active in lesions and to discover new diagnostic/therapeutic targets. Although the host response plays a critical role in protection from leishmaniasis and promoting disease severity, there are still unexplained aspects in the mechanism of non-healing cutaneous lesions, which need biomarkers for both targeted- therapy and diagnosis. To address this, transcriptional profiling of the skin lesions obtained from BALB/c mice infected with Leishmania major and healthy skin from naïve mice were evaluated by bioinformatics analysis, and then the results were validated by Revers Transcriptase-PCR. Five genes among the up-regulated differentially expressed genes named FCGR4, CCL4, CXCL9, Arg1 and IL-1β were found to have relatively high diagnostic value for CL due to L. major. Pathway analysis revealed that Triggering Receptor Expressed On Myeloid Cells 1 (TREM1) signaling pathways are active in cutaneous lesions, providing new insights for the understanding and treatment of leishmaniasis.

摘要

利什曼病小鼠模型中的基因表达谱分析为了解病变中活跃的分子途径以及发现新的诊断/治疗靶点提供了有用信息。尽管宿主反应在预防利什曼病和促进疾病严重程度方面起着关键作用,但在不愈合皮肤病变的机制中仍存在一些无法解释的方面,这需要用于靶向治疗和诊断的生物标志物。为了解决这个问题,通过生物信息学分析评估了从感染硕大利什曼原虫的BALB/c小鼠获得的皮肤病变和未感染小鼠的健康皮肤的转录谱,然后通过逆转录聚合酶链反应验证了结果。在上调的差异表达基因FCGR4、CCL4、CXCL9、Arg1和IL-1β中发现有五个基因对硕大利什曼原虫引起的皮肤利什曼病具有相对较高的诊断价值。通路分析显示,髓系细胞表达的触发受体1(TREM1)信号通路在皮肤病变中活跃,为利什曼病的理解和治疗提供了新的见解。

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