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昼夜节律钟蛋白 PER1 对维持 Dahl 盐敏感性大鼠内皮素轴的调节很重要。

The circadian clock protein PER1 is important in maintaining endothelin axis regulation in Dahl salt-sensitive rats.

机构信息

Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.

Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.

出版信息

Can J Physiol Pharmacol. 2023 Mar 1;101(3):136-146. doi: 10.1139/cjpp-2022-0134. Epub 2022 Nov 30.

Abstract

Endothelin-1 (ET-1) is a peptide hormone that acts on its receptors to regulate sodium handling in the kidney's collecting duct. Dysregulation of the endothelin axis is associated with various diseases, including salt-sensitive hypertension and chronic kidney disease. Previously, our lab has shown that the circadian clock gene PER1 regulates ET-1 levels in mice. However, the regulation of ET-1 by PER1 has never been investigated in rats. Therefore, we used a novel model where knockout of was performed in Dahl salt-sensitive rat background (SS ) to test a hypothesis that PER1 regulates the ET-1 axis in this model. Here, we show increased renal ET-1 peptide levels and altered endothelin axis gene expression in several tissues, including the kidney, adrenal glands, and liver in SS compared with control SS rats. antisense lncRNA , which has previously been suggested to be regulated by PER1, was also altered in SS rats compared with control SS rats. These data further support the hypothesis that PER1 is a negative regulator of and is important in the regulation of the endothelin axis in a tissue-specific manner.

摘要

内皮素-1 (ET-1) 是一种肽类激素,通过其受体作用于肾脏集合管来调节钠的处理。内皮素轴的失调与各种疾病有关,包括盐敏感性高血压和慢性肾脏病。以前,我们的实验室已经表明,昼夜节律基因 PER1 调节小鼠中的 ET-1 水平。然而,PER1 对 ET-1 的调节从未在大鼠中进行过研究。因此,我们使用了一种新的模型,在 Dahl 盐敏感性大鼠背景 (SS ) 中敲除 ,以测试 PER1 是否在该模型中调节 ET-1 轴的假设。在这里,我们显示在 SS 大鼠与对照 SS 大鼠相比,肾脏 ET-1 肽水平增加,并且包括肾脏、肾上腺和肝脏在内的几种组织中的内皮素轴基因表达发生改变。先前已经表明受 PER1 调节的反义 lncRNA 也在 SS 大鼠中发生改变。这些数据进一步支持 PER1 是 的负调节剂的假设,并且以组织特异性方式在调节内皮素轴中很重要。

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