Development of the circadian clockwork in the kidney

TY - JOUR

T1 - Development of the circadian clockwork in the kidney

AU - Mészáros, Krisztina

AU - Pruess, Linda

AU - Szabó, Attila J.

AU - Gondan, Matthias

AU - Ritz, Eberhard

AU - Schaefer, Franz

PY - 2014/11/5

Y1 - 2014/11/5

N2 - The circadian molecular clock is an internal time-keeping system composed of centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of the clock machinery in the developing kidney. Pregnant rats were housed at 12-12 h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20 and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev-erbα, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene (αENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate the role of nutritional cues, the feeding pattern was modified postpartum. Clock, Rev-erbα, Per2, αENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1 expression, while disrupting oscillations of the other genes. After weaning, oscillation phases shifted back toward the adult pattern, which was fully expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in the late fetal and early postnatal kidney. During the nursing period, oscillations are entrained by nutritional cues. The coupling of the circadian expression of tubular regulators of fluid and electrolyte excretion to the feeding-entrained clockwork may be important to maintain homeostasis during this critical period.

AB - The circadian molecular clock is an internal time-keeping system composed of centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of the clock machinery in the developing kidney. Pregnant rats were housed at 12-12 h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20 and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev-erbα, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene (αENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate the role of nutritional cues, the feeding pattern was modified postpartum. Clock, Rev-erbα, Per2, αENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1 expression, while disrupting oscillations of the other genes. After weaning, oscillation phases shifted back toward the adult pattern, which was fully expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in the late fetal and early postnatal kidney. During the nursing period, oscillations are entrained by nutritional cues. The coupling of the circadian expression of tubular regulators of fluid and electrolyte excretion to the feeding-entrained clockwork may be important to maintain homeostasis during this critical period.

KW - circadian rhythm

KW - clock genes

KW - development

KW - food

KW - kidney

KW - rat

U2 - 10.1038/ki.2014.199

DO - 10.1038/ki.2014.199

M3 - Journal article

SN - 0085-2538

VL - 86

SP - 915

EP - 922

JO - Kidney International

JF - Kidney International

IS - 5

ER -