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