The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice
Open accessAbstract
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.
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PER1 plays an important role in blood pressure maintenance by regulating aldosterone levels and affecting sodium retention.
“PER1 plays an important role in BP maintenance by regulating aldosterone levels and affecting sodium retention (71)(72)(73).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [72]
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Self-citation
- Authors
- Gumz, M. L., Stow, L. R., Lynch, I. J., Greenlee, M. M., Rudin, A., Cain, B. D., Weaver, D. R., & Wingo, C. S.
- Affiliations
- Malcom Randall VA Medical Center (US)
- University of Florida (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Wingo, Charles S.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-08-03
- Volume
- 119
- Issue
- 8
- Pages
- 2423-2434
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2719945
- OpenAlex
- W2122376672
- Cited by
- 216
- References
- 53
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 10 · 2021: 18 · 2020: 7 · 2019: 16 · 2018: 14 · 2017: 10 · 2016: 16 · 2015: 14 · 2014: 15 · 2013: 21 · 2012: 15
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007518, R01DK082680, R01DK049750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- circadian clock, epithelial sodium channel, alpha-ENaC, aldosterone, renal sodium transport, medullary collecting duct, circadian gene expression, sodium balance, sodium excretion, RNA silencing
- MeSH terms
- Aldosterone, Animals, Cells, Cultured, Circadian Rhythm, Gene Expression Regulation, Kidney, Male, Receptors, Glucocorticoid, RNA, Messenger, Sodium, Rats, Sprague-Dawley, Receptors, Mineralocorticoid, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Mice, Rats, Epithelial Sodium Channels, Period Circadian Proteins
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