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Molecular clock is involved in predictive circadian adjustment of renal function.

Authors
  • Zuber, Annie Mercier1
  • Centeno, Gabriel
  • Pradervand, Sylvain
  • Nikolaeva, Svetlana
  • Maquelin, Lionel
  • Cardinaux, Léonard
  • Bonny, Olivier
  • Firsov, Dmitri
  • 1 Department of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland. , (Switzerland)
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Sep 22, 2009
Volume
106
Issue
38
Pages
16523–16528
Identifiers
DOI: 10.1073/pnas.0904890106
PMID: 19805330
Source
Medline
Language
English
License
Unknown

Abstract

Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.

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