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基于微阵列的自身免疫性肝炎小鼠模型的转录谱分析。

Microarray-based transcriptional profiling of a mouse model of autoimmune hepatitis.

机构信息

College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, China.

Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, China.

出版信息

FEBS Open Bio. 2020 Oct;10(10):2040-2054. doi: 10.1002/2211-5463.12953. Epub 2020 Sep 19.

Abstract

Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not typically code for a protein. lncRNAs have regulatory roles in many physiological processes, and their dysregulation can contribute to cancer, cardiovascular and neurodegenerative diseases, as well as the onset of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. However, lncRNA expression changes in autoimmune hepatitis (AIH), a form of inflammation induced by immunological tolerance disorders, are poorly understood. Here, for the first time to our knowledge, we used microarrays to profile 1161 differentially expressed lncRNAs (DELs; 608 up- and 553 down-regulated) and 11 512 differentially expressed mRNAs (DEMs; 5189 up- and 6323 down- regulated) in a concanavalin A-induced AIH mouse model. We used quantitative real-time PCR to confirm the expression of eight DELs and DEMs, and analyzed the coexpression relationship between them. Potential biological functions of screened DELs and DEMs were predicted with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. DEL-DEM interaction networks were also constructed. Our study revealed the roles of DELs and DEMs in the pathogenesis of AIH. We also provided potential candidate biomarkers that may have potential for future development into possible diagnostics or as a treatment for this disorder.

摘要

长链非编码 RNA(lncRNA)是指长度大于 200 个核苷酸的 RNA 分子,通常不编码蛋白质。lncRNA 在许多生理过程中具有调节作用,其失调可能导致癌症、心血管和神经退行性疾病,以及自身免疫性疾病的发生,包括系统性红斑狼疮和类风湿关节炎。然而,自身免疫性肝炎(AIH)中 lncRNA 表达的变化,这种炎症是由免疫耐受紊乱引起的,人们对此知之甚少。在这里,我们首次使用微阵列技术对伴刀豆球蛋白 A 诱导的 AIH 小鼠模型中的 1161 个差异表达的长链非编码 RNA(DEL;608 个上调和 553 个下调)和 11512 个差异表达的 mRNA(DEM;5189 个上调和 6323 个下调)进行了分析。我们使用定量实时 PCR 技术对 8 个 DEL 和 DEM 的表达进行了验证,并分析了它们之间的共表达关系。通过基因本体论和京都基因与基因组百科全书分析预测了筛选出的 DEL 和 DEM 的潜在生物学功能。还构建了 DEL-DEM 相互作用网络。我们的研究揭示了 DEL 和 DEM 在 AIH 发病机制中的作用。我们还提供了潜在的候选生物标志物,这些标志物可能具有未来开发为这种疾病的潜在诊断或治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f017/7530384/03c17ec59e2b/FEB4-10-2040-g001.jpg

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