The Circadian Clock in the Mammalian Kidney

Abstract

Healthy circadian rhythms are important for maintaining overall health. Several core clock genes, including Bmal1, Per, CLOCK, and Cry encode transcription factors that regulate gene expression in the kidney and in nearly all other organs and cell types. Modulation of clock genes can cause major physiological effects. Loss of any of the core clock genes in mice results in significant changes in blood pressure, indicating that the molecular clock is critical for regulation of blood pressure. The kidney regulates electrolyte and volume balance and is thus an important regulator of blood pressure. Several lines of evidence suggest a role for the kidney clock in blood pressure regulation.

Many aspects of renal function, including glomerular filtration rate and electrolyte excretion, are known to vary with a circadian rhythm. Multiple studies have demonstrated that the kidney is sensitive to food and light cues, consistent with a role for circadian rhythms in the regulation of renal function. In the kidney, clock genes are rhythmically expressed and thousands of genes that contribute to renal function are subject to transcriptional regulation by the core clock proteins. Indeed, several key circadian genes oscillate even in the fetal kidney. It is clear that the circadian clock is an important regulator of renal function and that a better understanding of how it functions can open up new avenues for the treatment of kidney disease and hypertension.