Kid-1 participates in regulating ERK phosphorylation as a part of the circadian clock output in rat kidney

Abstract

Circadian clock genes play a role for the regulation of cell cycle, but the factors connecting clock to cell cycle are not fully understood. We found that mRNA of Kid-1— a zinc-finger-type transcriptional repressor was localized to cortical and juxtamedullary segments of tubules but not to glomeruli in the rat kidney. Kid-1 mRNA showed robust circadian oscillation with a peak at ZT16. Under temporal restricted feeding, the phase of the oscillation shifted along with mRNAs of the clock genes—Per1 and Per2. The rhythm of S-phase in cell cycle disappeared in the kidney under the restricted feeding. The level of phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was rhythmic with a peak at ZT16 in the kidney. We found that knockdown and overexpression of Kid-1 in NRK52E (normal rat kidney epithelial) cells induced and reduced the phosphorylation of ERK1/2, respectively. The data suggest that clock-controlled Kid-1 regulates the cell cycle of proliferating renal tubular epithelial cells through ERK phosphorylation.

Keywords::

• Circadian rhythm
• ERK
• Per1
• Per2
• Zinc-finger

Acknowledgments

This research was supported by the Grant-in-Aid for Scientific Research, the Takeda science foundation, and the Uehara memorial foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.