Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats.
Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats.
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DOI：
10.1152/ajprenal.00354.2004
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发表时间：
2005-09
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影响因子：
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通讯作者：
JM Seubert;JP Graves;JB Collins;SO Sieber;RS Paules;DL Kroetz;DC Zeldin
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文献类型：
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作者：
JM Seubert;JP Graves;JB Collins;SO Sieber;RS Paules;DL Kroetz;DC Zeldin
高血压的发展源于环境和遗传因素，其中肾脏起着核心作用。自发性高血压大鼠（SHR）和非高血压的Wistar-Kyoto（WKY）对照被广泛用作研究高血压的模型。本研究检测了SHR和WKY在高血压前期（3周龄）和高血压期（9周龄）的肾脏基因表达谱。此外，年龄相关的基因表达模式的变化进行了检查，从3至9周的WKY和SHR。将同一实验组的5至6个个体肾脏样品合并在一起，并使用国立环境健康科学研究所大鼠2.0版芯片进行四倍体杂交，该芯片含有约6，700个基因。在3周龄时，SHR和WKY之间有22个基因差异表达，在9周龄时有104个基因差异表达。可溶性环氧化物水解酶（Ephx 2）被发现在SHR在两个时间点显著上调，是主要的离群值。相反，弹性蛋白酶1（Ela 1）被认为是主要基因下调SHR在这两个时间点。在3与9周龄的档案分析确定了508差异表达的基因在WKY大鼠。相比之下，只有211个基因被发现在这段时间内在SHR中差异表达。在年龄相关分析中观察到的基因表达模式的改变表明SHR和WKY肾脏之间的血管细胞外基质系统存在显着差异。总之，我们的数据突出了高血压的复杂性以及参与这种疾病并受其影响的众多基因。
Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage (3 wk of age) and hypertensive stage (9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains approximately 6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase (Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 (Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition.