Screening of genes associated with inflammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases.
Screening of genes associated with inflammatory responses in the endolymphatic sac reveals underlying mechanisms for autoimmune inner ear diseases.
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筛选与内淋巴囊炎症反应相关的基因揭示自身免疫性内耳疾病的潜在机制
DOI：
10.3892/etm.2018.6479
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发表时间：
2018-09
影响因子：
2.7
通讯作者：
Xu A
中科院分区：
文献类型：
--
作者：
Zhang J;Wang N;Xu A
目前的研究分析了大鼠内淋巴囊(ES)的基因表达谱，并确定了在人类和大鼠ES中存在的表达基因，以揭示炎症反应的关键枢纽。微阵列数据(登录号：E-MEXP-3022)来自欧洲生物信息学研究所数据库，包括ES+硬脑膜组织的三个生物副本和大鼠纯硬脑膜组织的三个副本。采用基因芯片数据线性模型方法筛选差异表达基因(DEG)，利用互作基因/蛋白质数据库检索工具的数据构建蛋白质-蛋白质相互作用(PPI)网络，然后通过重叠邻域扩展聚类进行模块分析。使用注释、可视化和集成发现在线数据库工具进行功能丰富分析。共鉴定出612个差异表达基因，包括396个上调基因和216个下调基因。基因本体论术语丰富分析表明，DEGS与细胞黏附相关，包括α5-整合素(ITGA1)和分泌型磷蛋白1(SPP1)；T细胞共刺激，包括C-C趋化因子配体(CCL21和CCL19)；以及Toll样受体信号通路，包括Toll样受体(TLR2)、TLR7和TLR8。这些结论得到了京都百科全书基因和基因组路径分析的支持，这些分析揭示了细胞外基质-受体相互作用，包括ItGa1和Spp1；白细胞跨内皮细胞迁移，包括claudin-4(Cldn4)；以及疟疾，包括TLR2。通过计算PPI网络的三个拓扑属性，揭示了Itga1、CD24和Spp1的枢纽作用。根据相应的阈值进行显著的模块分析后，CCL21、Ccl19和Cldn4被证明是至关重要的，这表明它们富含在炎症途径中。TLR7、TLR2、颗粒酶m和TLR8是与大鼠和人ES的炎症反应相关的常见基因。综上所述，上述炎症相关基因的异常表达可能与自身免疫性内耳疾病的发生有关。
The current study analyzed gene expression profiles of the endolymphatic sac (ES) in rats and identified expressed genes, present in the human and rat ES, to reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP-3022) were obtained from the European Bioinformatics Institute database, including three biological replicates of ES plus dura tissues and three replicates of pure dura tissues form rats. Differentially expressed genes (DEGs) were screened using the Linear Model for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins database followed by a module analysis via Clustering with Overlapping Neighborhood Expansion. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A total of 612 DEGs were identified, including 396 upregulated and 216 downregulated genes. Gene ontology term enrichment analysis indicated DEGs were associated with cell adhesion, including α5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co-stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8. These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes pathway analyses revealing extracellular matrix-receptor interaction, including Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4); and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed by calculating three topological properties of the PPI network. Ccl21, Ccl19 and Cldn4 were demonstrated to be crucial following significant module analysis according to the corresponding threshold, which revealed they were enriched in inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes associated with inflammatory responses in rat and human ES. In conclusion, abnormal expression of the aforementioned inflammation-associated genes may be associated with the development of autoimmune inner ear diseases.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
6.1
作者：
Cai, Qunfeng;Patel, Minal;Coling, Donald;Hu, Bo Hua
通讯作者：
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影响因子：
2.6
作者：
Lin, Chang-Fu;Lee, Kuan-Ji;Lin, Yung-Song
通讯作者：
Lin, Yung-Song
影响因子：
2.6
作者：
Moller, Martin Nue;Kirkeby, Svend;Caye-Thomasen, Per
通讯作者：
Caye-Thomasen, Per
影响因子：
2.1
作者：
Huang, Natalie C.;Sataloff, Robert T.
通讯作者：
Sataloff, Robert T.