NOVEL GENES IN BRAIN TISSUES OF EAE-INDUCED NORMAL AND OBESE MICE: UPREGULATION OF METAL ION-BINDING PROTEIN GENES IN OBESE-EAE MICE

NOVEL GENES IN BRAIN TISSUES OF EAE-INDUCED NORMAL AND OBESE MICE: UPREGULATION OF METAL ION-BINDING PROTEIN GENES IN OBESE-EAE MICE
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DOI:
10.1016/j.neuroscience.2016.12.002
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发表时间:
2017-02-20
期刊:
影响因子:
3.3
通讯作者:
Kwon, Oh-Seung
Kwon, Oh-Seung
中科院分区:
医学3区
文献类型:
--
作者:
Hasan, Mahbub;Seo, Ji-Eun;Kwon, Oh-Seung

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实验性自身免疫性脑脊髓炎(Experimental autoimmune encephalomyelitis,EAE)是一种由髓鞘变性引起的中枢神经系统炎症性自身免疫性疾病。本研究旨在鉴定EAE诱导的正常饮食(ND)小鼠和高脂饮食(HFD)诱导的肥胖小鼠脑中差异表达的基因(DEG),并鉴定负责阐明疾病机制的新基因。从脑组织中纯化的mRNA样品进行基因芯片分析,并通过实时RT-PCR验证。如果观察到大于1.5倍或小于0.66倍的显著变化,则鉴定DEG(p < 0.05)。使用基因和基因组途径的京都百科全书和基因本体(GO)分析进行途径构建和功能分类。HFD-EAE小鼠表现出比ND-EAE小鼠更严重的疾病症状。从GO研究中,HFD-EAE到ND-EAE基因的倍数变化表明这些基因与免疫应答、抗原呈递和补体激活相关的途径显著相关。金属离子结合蛋白相关基因在HFD-EAE和NDEAE小鼠中表达上调。HFD-EAE小鼠中Cul 9、Mast 2和C4 b表达的上调显著高于ND-EAE小鼠。Cul 9、Mast 2、C4 b、Psmb 8、Ly 86和Ms 4a 6d在ND-和HFD-EAE小鼠中均显著上调。Fcgr 4、S3-12、Gca和Zdhhc 4仅在ND-EAE中上调,XIr 4 b仅在HFD-EAE小鼠中上调。金属离子结合蛋白Cul 9和Mast 2基因在HFD-EAE小鼠中表达显著上调。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system resulting from degeneration of the myelin sheath. This study is aimed to identify differentially expressed genes (DEGs) in the brain of EAE-induced normal diet (ND) mice and high-fat diet (HFD)-induced obese mice, and to identify novel genes responsible for elucidating the mechanism of the disease. Purified mRNA samples from the brain tissue were analyzed for gene microarray and validated by real-time RT-PCR. DEGs were identified if significant changes greater than 1.5-fold or less than 0.66-fold were observed (p < 0.05). Pathway construction and functional categorization were performed using the Kyoto encyclopedia of genes and genomes pathways and gene ontology (GO) analysis. HFD-EAE mice showed more severe disease symptoms than ND-EAE mice. From GO study, fold changes of HFD-EAE to ND-EAE genes indicated that the genes were significantly associated to the pathways related with the immune response, antigen presentation, and complement activation. The genes related with metal ion binding proteins were upregulated in HFD-EAE and NDEAE mice. Upregulation of Cul9, Mast2, and C4b expression is significantly higher in HFD-EAE mice than ND-EAE mice. Cul9, Mast2, C4b, Psmb8, Ly86, and Ms4a6d were significantly upregulated in both ND- and HFD-EAE mice. Fcgr4, S3-12, Gca, and Zdhhc4 were upregulated only in ND-EAE, and XIr4b was upregulated only in HFD-EAE mice. And significant upregulated genes of metal ion-binding proteins (Cul9 and Mast2) were observed in HFD-EAE mice. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.