UMMS Affiliation

Department of Neurobiology; Weaver Lab

Date

8-2009

Document Type

Article

Medical Subject Headings

Aldosterone; Animals; Cells, Cultured; Circadian Rhythm; Epithelial Sodium Channel; Gene Expression Profiling; *Gene Expression Regulation; Intracellular Signaling Peptides and Proteins; Kidney; Male; Mice; Period Circadian Proteins; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Sodium

Disciplines

Neuroscience and Neurobiology

Abstract

The mineralocorticoid aldosterone is a major regulator of sodium transport in target epithelia and contributes to the control of blood pressure and cardiac function. It specifically functions to increase renal absorption of sodium from tubular fluid via regulation of the alpha subunit of the epithelial sodium channel (alphaENaC). We previously used microarray technology to identify the immediate transcriptional targets of aldosterone in a mouse inner medullary collecting duct cell line and found that the transcript induced to the greatest extent was the circadian clock gene Period 1. Here, we investigated the role of Period 1 in mediating the downstream effects of aldosterone in renal cells. Aldosterone treatment stimulated expression of Period 1 (Per1) mRNA in renal collecting duct cell lines and in the rodent kidney. RNA silencing of Period 1 dramatically decreased expression of mRNA encoding alphaENaC in the presence or absence of aldosterone. Furthermore, expression of alphaENaC-encoding mRNA was attenuated in the renal medulla of mice with disruption of the Per1 gene, and these mice exhibited increased urinary sodium excretion. Renal alphaENaC-encoding mRNA was expressed in an apparent circadian pattern, and this pattern was dramatically altered in mice lacking functional Period genes. These results suggest a role for Period 1 in the regulation of the renal epithelial sodium channel and more broadly implicate the circadian clock in control of sodium balance.

Comments

Citation: J Clin Invest. 2009 Aug;119(8):2423-34. doi: 10.1172/JCI36908. Epub 2009 Jul 1. Link to article on publisher's site

Publisher PDF posted as allowed by the publisher's author rights policy at http://static.the-jci.org/content_assets/admin/forms/jcicopyright.pdf.

Related Resources

Link to Article in PubMed

PubMed ID

19587447

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.