Fkbp51基因敲除小鼠心脏与肝脏RNA表达谱系的分析比较

发布时间：2018-01-27 02:31

本文关键词： Fkbp基因敲除小鼠心脏肝脏代谢基因表达信号通路　出处：《中国比较医学杂志》2017年07期 　论文类型：期刊论文

【摘要】：目的通过分析野生型小鼠(WT)和Fkbp51基因敲除(KO)小鼠心脏与肝RNA表达谱系之间的差异,研究Fkbp51基因在心脏和肝组织代谢通路中的作用。方法利用第二代高通量基因测序技术,对Fkbp51 KO和WT小鼠的心脏和肝进行mRNA表达谱测序,将心脏测序的数据结果用DEGseq进行差异分析,肝脏组织测序结果用BRB-Array Tools进行分析,分别筛选出小鼠心脏和肝的差异基因,利用在线工具DAVID对差异基因进行GO本体分析和KEGG通路分析,利用Bioinfo GP数据库的Venn工具分析两种组织的共差异基因,利用STRING数据库对蛋白质的互作网络进行分析。结果 (1)Fkbp51的缺失导致心脏中血管平滑肌收缩、趋化因子信号、视黄醇信号和MAPK信号等相关通路的mRNA表达发生改变;(2)Fkbp51的缺失导致肝组织中胆固醇合成及代谢、脂类代谢以及氧化还原等相关基因和通路的变化;(3)在心脏和肝组织中,Fkbp51缺失造成了4个共差异基因,其中Rnaset2b、Hmga1和Fkbp51下调,而Cyp2b10在心脏组织中下调,在肝组织中上调。这些蛋白均可与HSP90蛋白相互作用,参与心脏和肝组织中的代谢。结论 Fkbp51在心脏和肝中参与不同的代谢及基因表达调控通路,其作用既是相互独立又是相互联系的。
[Abstract]:Objective to analyze the difference of RNA expression lineages between the heart and liver of wild type mice and Fkbp51 knockout mice. Methods the second generation high-throughput gene sequencing technique was used to study the role of Fkbp51 gene in the metabolic pathway of heart and liver tissues. The heart and liver of Fkbp51 KO and WT mice were sequenced by mRNA expression profile. The results of heart sequencing were analyzed by DEGseq. The results of liver tissue sequencing were analyzed by BRB-Array Tools, and the differentially expressed genes in heart and liver of mice were screened respectively. The differential genes were analyzed by go ontology analysis and KEGG pathway analysis using online tool DAVID, and the co-differential genes of the two tissues were analyzed by Venn tools of Bioinfo GP database. The STRING database was used to analyze the protein interaction network. Results the absence of Fkbp51 resulted in the contraction of vascular smooth muscle and the chemokine signal in the heart. The mRNA expression of retinol signal and MAPK signal were changed. The deletion of Fkbp51 leads to the changes of cholesterol synthesis and metabolism, lipid metabolism, redox and other related genes and pathways in liver tissue. The deletion of Fkbp51 in heart and liver resulted in four co-differentially expressed genes, among which Rnaset2bhmga1 and Fkbp51 were down-regulated. Cyp2b10 is down-regulated in heart tissue and up-regulated in liver tissue. These proteins interact with HSP90 protein. Conclusion Fkbp51 is involved in different metabolism and gene expression regulation pathways in heart and liver.
【作者单位】：中国医学科学院医学实验动物研究所北京协和医学院比较医学中心卫生部人类疾病比较医学重点实验室国家中医药管理局人类疾病动物模型三级实验室;
【基金】：北京市自然科学基金资助项目(NO.7164278) 国家科技重大专项(NO.2014ZX10004002-003-001) 国家自然科学基金(NO.81272273) 中央级公益性科研院所基本科研业务费(NO.DWS201508,DWS201607)
【分类号】：R3416
【正文快照】： 共同通讯FK506结合蛋白(FK506 binding proteins,FKBPs)是一类具有肽基脯氨酰顺反异构酶活性的蛋白分子,参与细胞内蛋白折叠的修饰过程[1]。这类蛋白能够通过其TPR结构域直接与热休克蛋白HSP90结合,参与甾体类激素受体复合物的形成和功能调节[2]。1993年人们首次发现了Fkbp51(

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