Abstract: FR-OR127

Robust Circadian Clock Oscillation and Osmotic Rhythms in the Inner Medulla Reflecting Cortico-Medullary Osmotic Gradient Rhythm in Rodent Kidney

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 702 Water/Urea/Vasopressin, Organic Solutes

Authors

  • Hara, Masayuki, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Minami, Yoichi, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Koike, Nobuya, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Kusaba, Tetsuro, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Tamagaki, Keiichi, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Yagita, Kazuhiro, Kyoto Prefectural University of Medicine, Kyoto, Japan
Background

Circadian clocks in mammals function in most organs and tissues throughout the body. Various renal functions such as the glomerular filtration and excretion of electrolytes exhibit circadian rhythms. Although it has been reported that the expression of the clock genes composing molecular oscillators show apparent daily rhythms in rodent kidneys, functional variations of regional clocks are not yet fully understood.

Methods

1. To monitor the molecular clock work and localization, we applied the macroscopic bioluminescence imaging method of the PER2::Luciferase knock-in mouse kidney. 2. We analyzed the circadian fluctuation of the cortico-medullary osmotic pressure gradient. 3. We analyzed diurnal expression patterns of genes contributing to high osmotic pressure and reabsorption of water in mice kidneys. 4. To analyze the effect of molecular clock on diurnal variations of osmotic pressure gradient, we measured osmotic pressure gradient in systemic Bmal1 deficient mice which completely lack a functional clock.

Results

1. PER2::Luciferase knock-in mice exhibited strong and robust circadian clock oscillation in the medulla. 2. Significant diurnal rhythm of the tissue osmolality with peaking at night (active phase) was found in the medulla but not in the cortex. This suggests that cortico-medullary osmotic pressure gradient changes diurnally depending on osmotic pressure rhythm in the inner medulla. 3. Vasopressin receptors (V1aR, V2R), urea transporter (UT-A2) and water channel (Aqp2) show diurnal variations in the inner medulla. 4. Systemic Bmal1 deficient mice impaired circadian rhythm of osmotic pressure gradient and of expression of genes (V1aR, V2R, UT-A2, and Aqp2) in the inner medulla.

Conclusion

The circadian clocks in the medulla of the kidney regulate the circadian rhythm of gene expressions related to the water reabsorption and subsequent cortico-medullary osmotic pressure gradient, resulting in the physiological day-night rhythm of urination.