Fkbp51基因敲除小鼠心脏与肝脏RNA表达谱系的分析比较

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。

Analysis and comparison of RNA expression profiles in the heart and liver of Fkbp51 knockout mice

Objective To study the function of Fkbp51 in the heart and liver by analyzing the differential RNA expression profiles in the wild-type mice (WT) and Fkbp51 knockout (KO) mice, and to elucidate the role of Fkbp51 gene in metabolic pathways in the heart and liver. Methods Using the second generation of high-throughput gene sequencing technology, the mRNA expression profiles of heart and liver were sequenced in WT and Fkbp51 KO mice. The data of sequencing of heart tissues were analyzed by DEGseq, and the results of sequencing of liver tissues were analyzed by BRB-Array Tools. The differential genes of the heart and liver in the mice were screened respectively. Gene ontology (GO) analysis and KEGG pathway analysis were performed to analyze the differentially expressed genes using the online tool DAVID. In addition, the differential genes of the two organ tissues were analyzed by Venn diagram. The interaction network of proteins was analyzed using the STRING database. Results (1) The absence of Fkbp51 led to changes in mRNA expressions of heart-related signal pathways such as vascular smooth muscle contraction, chemokine, retinol, and MAPK signaling pathways. (2) The lack of Fkbp51 mostly induced changes in cholesterol synthesis and metabolism, lipid metabolism, redox and other related genes and pathways in the liver. (3) In the heart and liver, Fkbp51 deletionresult ed in four co-differential genes, among them, down-regulation of Rnaset2b, Hmga1 and Fkbp51, while Cyp2b10 was down-regulated in the heart but up-regulated in the liver. All these proteins may interact with HSP90 protein and participat in the metabolism of heart and liver tissues. Conclusions Fkbp51 is involved in different metabolic and gene expression regulation pathways of heart and liver, and the roles are both independent and interrelated.