Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats
Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats
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DOI：
10.1152/physiolgenomics.00031.2008
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发表时间：
2008-06-12
影响因子：
4.6
通讯作者：
Cowley, Allen W., Jr.
中科院分区：
文献类型：
--
作者：
Liang, Mingyu;Lee, Norman H.;Cowley, Allen W., Jr.
Dahl盐敏感（SS）大鼠是一种广泛使用的人类盐敏感性高血压和肾损伤模型。我们研究了SS模型中复杂疾病表型背后的分子网络，使用的设计涉及两种受盐诱导高血压保护的consomic大鼠品系和一种不受保护的大鼠品系。将挪威棕（BN）13或18号染色体（而不是20号染色体）替换到SS基因组中可显著减轻盐诱导的高血压和蛋白尿。用共240个cDNA微阵列检测了SS大鼠和SS-13（BN）、SS-18（BN）和SS-20（BN）大鼠肾脏中的基因表达谱。在0.4%盐饮食的consomic品系和SS大鼠之间差异表达的基因中，被取代的染色体被过度表达。F5、Serpinc 1、Slc 19 a2以及位于第13号染色体上的其他3个表达序列标签（EST）所代表的基因在SS-13（BN）和所有其他检测菌株之间存在差异表达。同样地，位于18号染色体上的ESTs，B4 galt 6，Colec 12，Hsd 17 b4和其他5个ESTs也表现出SS-18（BN）特有的表达模式。暴露于4%盐饮食时，在肾皮质中有184个EST，在肾髓质中有346个EST，其中SS-13（BN）和SS-18（BN）共享一种表达模式，而SS和SS-20（BN）共享另一种表达模式，反映了四种菌株之间的表型分离。分子网络，可能有助于发展达尔盐敏感性高血压和蛋白尿的方法，合并生物学知识驱动的分析和数据驱动的贝叶斯概率分析。
The Dahl salt-sensitive (SS) rat is a widely used model of human salt-sensitive hypertension and renal injury. We studied the molecular networks that underlie the complex disease phenotypes in the SS model, using a design that involved two consomic rat strains that were protected from salt-induced hypertension and one that was not protected. Substitution of Brown Norway (BN) chromosome 13 or 18, but not 20, into the SS genome was found to significantly attenuate salt-induced hypertension and albuminuria. Gene expression profiles were examined in the kidneys of SS and consomic SS-13(BN), SS-18(BN), and SS-20(BN) rats with a total of 240 cDNA microarrays. The substituted chromosome was overrepresented in genes differentially expressed between a consomic strain and SS rats on a 0.4% salt diet. F5, Serpinc1, Slc19a2, and genes represented by three other expressed sequence tags ( ESTs), which are located on chromosome 13, were found to be differentially expressed between SS-13(BN) and all other strains examined. Likewise, Acaa2, B4galt6, Colec12, Hsd17b4, and five other ESTs located on chromosome 18 exhibited expression patterns unique to SS-18(BN). On exposure to a 4% salt diet, there were 184 ESTs in the renal cortex and 346 in the renal medulla for which SS-13(BN) and SS-18(BN) shared one expression pattern, while SS and SS-20(BN) shared another, mirroring the phenotypic segregation among the four strains. Molecular networks that might contribute to the development of Dahl salt-sensitive hypertension and albuminuria were constructed with an approach that merged biological knowledge-driven analysis and data-driven Bayesian probabilistic analysis.