本文關(guān)鍵詞： Fkbp基因敲除小鼠 心臟 肝臟 代謝 基因表達(dá) 信號(hào)通路　出處：《中國比較醫(yī)學(xué)雜志》2017年07期 　論文類型：期刊論文

【摘要】：目的通過分析野生型小鼠(WT)和Fkbp51基因敲除(KO)小鼠心臟與肝RNA表達(dá)譜系之間的差異,研究Fkbp51基因在心臟和肝組織代謝通路中的作用。方法利用第二代高通量基因測(cè)序技術(shù),對(duì)Fkbp51 KO和WT小鼠的心臟和肝進(jìn)行mRNA表達(dá)譜測(cè)序,將心臟測(cè)序的數(shù)據(jù)結(jié)果用DEGseq進(jìn)行差異分析,肝臟組織測(cè)序結(jié)果用BRB-Array Tools進(jìn)行分析,分別篩選出小鼠心臟和肝的差異基因,利用在線工具DAVID對(duì)差異基因進(jìn)行GO本體分析和KEGG通路分析,利用Bioinfo GP數(shù)據(jù)庫的Venn工具分析兩種組織的共差異基因,利用STRING數(shù)據(jù)庫對(duì)蛋白質(zhì)的互作網(wǎng)絡(luò)進(jìn)行分析。結(jié)果 (1)Fkbp51的缺失導(dǎo)致心臟中血管平滑肌收縮、趨化因子信號(hào)、視黃醇信號(hào)和MAPK信號(hào)等相關(guān)通路的mRNA表達(dá)發(fā)生改變;(2)Fkbp51的缺失導(dǎo)致肝組織中膽固醇合成及代謝、脂類代謝以及氧化還原等相關(guān)基因和通路的變化;(3)在心臟和肝組織中,Fkbp51缺失造成了4個(gè)共差異基因,其中Rnaset2b、Hmga1和Fkbp51下調(diào),而Cyp2b10在心臟組織中下調(diào),在肝組織中上調(diào)。這些蛋白均可與HSP90蛋白相互作用,參與心臟和肝組織中的代謝。結(jié)論 Fkbp51在心臟和肝中參與不同的代謝及基因表達(dá)調(diào)控通路,其作用既是相互獨(dú)立又是相互聯(lián)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.
【作者單位】： 中國醫(yī)學(xué)科學(xué)院醫(yī)學(xué)實(shí)驗(yàn)動(dòng)物研究所北京協(xié)和醫(yī)學(xué)院比較醫(yī)學(xué)中心衛(wèi)生部人類疾病比較醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室國家中醫(yī)藥管理局人類疾病動(dòng)物模型三級(jí)實(shí)驗(yàn)室;
【基金】：北京市自然科學(xué)基金資助項(xiàng)目(NO.7164278) 國家科技重大專項(xiàng)(NO.2014ZX10004002-003-001) 國家自然科學(xué)基金(NO.81272273) 中央級(jí)公益性科研院所基本科研業(yè)務(wù)費(fèi)(NO.DWS201508,DWS201607)
【分類號(hào)】：R3416
【正文快照】： 共同通訊FK506結(jié)合蛋白(FK506 binding proteins,FKBPs)是一類具有肽基脯氨酰順反異構(gòu)酶活性的蛋白分子,參與細(xì)胞內(nèi)蛋白折疊的修飾過程[1]。這類蛋白能夠通過其TPR結(jié)構(gòu)域直接與熱休克蛋白HSP90結(jié)合,參與甾體類激素受體復(fù)合物的形成和功能調(diào)節(jié)[2]。1993年人們首次發(fā)現(xiàn)了Fkbp51(

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