Molecular clock is involved in predictive circadian adjustment of renal function
| Autor: | Annie Mercier Zuber, Olivier Bonny, Svetlana Nikolaeva, Sylvain Pradervand, Dmitri Firsov, Gabriel Centeno, Lionel Maquelin, Léonard Cardinaux |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Time Factors CLOCK Proteins Receptors Cytoplasmic and Nuclear Blood Pressure Nerve Tissue Proteins Biology Kidney Concentrating Ability Electrolytes Mice Biological Clocks Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Animals Circadian rhythm Distal convoluted tubule Kidney Tubules Collecting Oligonucleotide Array Sequence Analysis Aquaporin 4 Mice Knockout Kidney Aquaporin 2 Multidisciplinary NPAS2 Gene Expression Profiling Biological Sciences Connecting tubule Circadian Rhythm DNA-Binding Proteins Mice Inbred C57BL CLOCK Urodynamics Basic-Leucine Zipper Transcription Factors Kidney Tubules Endocrinology medicine.anatomical_structure Renal physiology Nuclear Receptor Subfamily 1 Group D Member 1 Trans-Activators Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:16523-16528 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0904890106 |
| Popis: | 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, αENaC). 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. |
| Databáze: | OpenAIRE |
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