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白细胞介素-9激活的星形胶质细胞和实验性自身免疫性脑脊髓炎小鼠中长链非编码RNA和信使核糖核酸表达谱分析

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice.

作者信息

Liu Xiaomei, Zhang Qing, Wang Weixiao, Zuo Dongjiao, Wang Jing, Zhou Feng, Niu Liping, Li Xiangyang, Qin Suping, Kou Yanbo, Kong Fanyun, Pan Wei, Wang Yugang, Gao Dianshuai, Sun Hong, Meves Jessica M, Zheng Kuiyang, Tang Renxian

机构信息

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology and Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, China.

出版信息

Cell Physiol Biochem. 2018;45(5):1986-1998. doi: 10.1159/000487975. Epub 2018 Mar 2.

Abstract

BACKGROUND/AIMS: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes.

METHODS

we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs.

RESULTS

Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays.

CONCLUSIONS

Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.

摘要

背景/目的:多发性硬化症(MS)是一种中枢神经系统的自身免疫性疾病,与脱髓鞘和轴突损伤有关。星形胶质细胞活化参与了MS的发病机制以及实验性自身免疫性脑脊髓炎(EAE),即MS的动物模型。本研究旨在寻找EAE小鼠和活化星形胶质细胞中的潜在长链非编码RNA(lncRNA)。

方法

我们对EAE小鼠脑组织和用白细胞介素-9(50纳克/毫升)处理的原代小鼠星形胶质细胞进行了lncRNA微阵列分析。通过实时定量聚合酶链反应验证了12种lncRNA。应用基因本体论和京都基因与基因组百科全书(KEGG)通路分析来探索lncRNA的潜在功能。

结果

EAE小鼠脑组织中有3300种lncRNA和3250种信使核糖核酸(mRNA)差异表达,活化星形胶质细胞中有3748种lncRNA和3332种mRNA差异表达。值得注意的是,在EAE小鼠脑组织和活化星形胶质细胞中均有2种共同上调的lncRNA和3种共同下调的lncRNA,包括Gm14005、Gm12478、小鼠lncRNA1117、AK080435和小鼠lncRNA0681,它们调节内质网钙流动力学、锌指蛋白和细胞凋亡。同样,在体内和体外均有7种mRNA共同上调和2种mRNA共同下调。基因本体论和KEGG通路分析表明,差异表达mRNA的生物学功能与代谢、发育和炎症相关。实时定量聚合酶链反应验证结果与微阵列数据一致。

结论

我们的数据揭示了lncRNA和mRNA在体内和体外的表达谱,这可能有助于阐明MS/EAE过程中星形胶质细胞活化的机制。

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