A study of the key genes and inflammatory signaling pathways involved in HLA-B27-associated acute anterior uveitis families.
A study of the key genes and inflammatory signaling pathways involved in HLA-B27-associated acute anterior uveitis families.
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HLA-B27相关急性前葡萄膜炎家族关键基因及炎症信号通路研究
DOI：
10.3892/ijmm.2018.3596
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发表时间：
2018-07
影响因子：
5.4
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Yu S;Mao C;Yu J;Qi X;Wang J;Lu H
本研究旨在探讨HLA-B27相关的急性前葡萄膜炎（AAU）家系的关键基因和炎症信号通路。本研究包括4个HLA-B27阳性AAU患者及其HLA-B27阳性血亲的家系。从受试者中分离外周血单核细胞并用脂多糖（LPS）刺激。采用基因表达谱芯片技术鉴定差异表达基因，并采用基因本体论（GO）、通路分析、信号网络分析和基因关系网络（Gene-Rel-Net）等生物信息学技术对差异表达基因进行分析。最后，ELISA用于定量上清液中的细胞因子。基因表达微阵列鉴定了801个DEG，包括349个上调基因和452个下调基因。GO分析揭示了几个重要的功能，包括代谢，免疫和炎症反应。途径分析强调了金黄色葡萄球菌感染、趋化因子和代谢信号传导途径的增强活性，以及精氨酸与细胞因子受体的相互作用。通过Signal-Net和Gene-Rel-Net分析发现18个DEG基因起关键作用，并通过定量聚合酶链反应（PCR）分析验证其为关键基因。总之，与健康HLA-B27阳性血亲的单核细胞相比，AUU患者的单核细胞对LPS刺激更敏感，并表现出更突出的炎症反应。这些特征性DEG可能为AAU的发病机制提供新的证据，并有助于确定新的治疗靶点。
The present study was conducted to investigate the key genes and the inflammatory signaling pathways involved in HLA-B27-associated acute anterior uveitis (AAU) families. Four families with HLA-B27-positive AAU patients and their HLA-B27-positive blood relatives were included in the study. Peripheral blood monocytes were isolated from the subjects and stimulated by lipopolysaccharides (LPS). Gene expression microarrays were used to identify the differentially expressed genes (DEGs), and the DEGs were analyzed by a range of bioinformatics-based techniques, including Gene Ontology (GO), Pathway analysis, Signal-Net analysis and Gene Relation Network (Gene-Rel-Net). Finally, ELISA was used to quantify cytokines in the supernatant. The gene expression microarrays identified 801 DEGs, including 349 upregulated and 452 downregulated genes. The GO analysis revealed several important functions, including metabolic, immune and inflammatory responses. The pathway analysis highlighted the enhanced activity of Staphylococcus aureus infection, chemokine and metabolic signaling pathways, as well as cytokine-to-cytokine receptor interactions. A total of 18 DEGs that were found to play critical roles by Signal-Net and Gene-Rel-Net and verified by quantitative polymerase chain reaction analysis were identified as key genes. In conclusion, monocytes from the AUU patients were more sensitive and exhibited a more prominent inflammatory response to stimulation by LPS compared with monocytes from healthy HLA-B27-positive blood relatives. These characterized DEGs may provide new evidence for the pathogenesis of AAU and help identify new therapeutic targets.
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影响因子：
15.8
作者：
McGonagle D;McDermott MF
通讯作者：
McDermott MF
影响因子：
3.7
作者：
Maldifassi MC;Atienza G;Arnalich F;López-Collazo E;Cedillo JL;Martín-Sánchez C;Bordas A;Renart J;Montiel C
通讯作者：
Montiel C
影响因子：
3.3
作者：
Deschenes, Jean;Murray, Philip I.;Nussenblatt, Robert B.
通讯作者：
Nussenblatt, Robert B.
影响因子：
5.8
作者：
Li, Caiyan;Li, Hongzhe
通讯作者：
Li, Hongzhe
影响因子：
--
作者：
Liu X;Hu X;Zhang X;Li Z;Lu H
通讯作者：
Lu H