The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes.
The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes.
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DOI：
10.1161/hypertensionaha.112.190892
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Gumz ML
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文献类型：
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作者：
Stow LR;Richards J;Cheng KY;Lynch IJ;Jeffers LA;Greenlee MM;Cain BD;Wingo CS;Gumz ML
昼夜节律时钟蛋白PER1参与调节基础水平的肾上皮钠通道α亚单位(αENaC)的表达，并对糖皮质激素醛固酮作出反应。本研究的目的是确定PER1在调节皮质集合管细胞中额外的肾脏钠处理基因中的作用，并评估缺乏PER1功能的小鼠的血压。为了确定PER1是否调节肾脏钠处理中的其他重要基因，采用了候选基因方法。将非靶向siRNA或PER1特异性siRNA导入永生化集合管细胞。Na，K-α酶活性的正向调节因子PER1ENaC和Fxyd5基因的表达在PER1ENaC和Fxyd5基因表达下调。相反，ENaC的负效应小窝蛋白-1、Ube2e3和ET-1在PER1基因敲除后被诱导表达。这些结果使我们评估了PER1KO小鼠的血压。与野生型动物相比，缺乏PER1的小鼠表现出显著的血压降低和肾脏ET-1水平升高。鉴于肾脏ET-1在ENaC抑制和血压控制中的既定作用，肾脏ET-1升高是PER1KO小鼠观察到的较低血压的一个可能解释。这些数据支持昼夜节律时钟蛋白PER1在参与肾脏钠重吸收的基因的协调调节中的作用。重要的是，与野生型相比，在PER1 KO小鼠中观察到的较低的血压表明PER1也在血压控制中发挥作用。
The circadian clock protein Period 1 (Per1) contributes to the regulation of expression of the α subunit of the renal epithelial sodium channel (αENaC) at the basal level and in response to the mineralocorticoid hormone aldosterone. The goals of the present study were to define the role of Per1 in the regulation of additional renal sodium handling genes in cortical collecting duct cells and to evaluate BP in mice lacking functional Per1. To determine if Per1 regulates additional genes important in renal sodium handling, a candidate gene approach was employed. Immortalized collecting duct cells were transfected with a non-target siRNA or a Per1 specific siRNA. Expression of the genes for αENaC and Fxyd5, a positive regulator of Na, K-ATPase activity, decreased in response to Per1 knockdown. Conversely, mRNA expression of caveolin-1, Ube2e3 and ET-1, all negative effectors of ENaC, was induced following Per1 knockdown. These results led us to evaluate BP in Per1 KO mice. Mice lacking Per1 exhibit significantly reduced BP and elevated renal ET-1 levels compared to wild type animals. Given the established role of renal ET-1 in ENaC inhibition and blood pressure control, elevated renal ET-1 is one possible explanation for the lower blood pressure observed in Per1 KO mice. These data support a role for the circadian clock protein Per1 in the coordinate regulation of genes involved in renal sodium reabsorption. Importantly, the lower BP observed in Per1 KO mice compared to wild type suggests a role for Per1 in BP control as well.