A Role for the Circadian Clock Protein Per1 in the Regulation of the NaCl Co-transporter (NCC) and the with-no-lysine Kinase (WNK) Cascade in Mouse Distal Convoluted Tubule Cells

Mar 11, 2014The Journal of biological chemistry

The circadian clock protein Per1 may regulate salt transport and related signaling proteins in kidney cells

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Abstract

Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of NCC and WNK1 but increased expression of WNK4 in the renal cortex of mice.

  • Per1 regulates sodium transport in the distal convoluted tubule (DCT) by modulating the expression of the NaCl co-transporter (NCC) and with-no-lysine kinases (WNKs).
  • Inhibition of Per1 nuclear entry led to decreased NCC protein expression and activity, indicating a functional impact on sodium reabsorption.
  • Chromatin immunoprecipitation experiments showed that Per1 interacts with the promoters of NCC, WNK1, and WNK4, suggesting transcriptional regulation.
  • Changes in short-lived heterogeneous nuclear RNA indicate that Per1 may affect gene expression dynamics in the DCT.

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