Evidence map›Paper›PMID 22832921›Full record

ArticleAmerican journal of physiology. Renal physiology2012

Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε.

Jacob Richards, Megan M Greenlee, Lauren A Jeffers, Kit-Yan Cheng, Laijing Guo, Douglas C Eaton, Michelle L Gumz

Abstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Mineralocorticoid Receptor and Sleep Quality in Chronic Kidney Disease.International journal of molecular sciences · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Autonomic nerves and circadian control of renal function.Autonomic neuroscience : basic & clinical · 2019
    Review
  11. Review
  12. Circadian clock-mediated regulation of blood pressure.Free radical biology & medicine · 2018
    Review
  13. Circadian regulation of renal function.Free radical biology & medicine · 2018
    Review
  14. Review
  15. Review
  16. High dietary sodium causes dyssynchrony of the renal molecular clock in rats.American journal of physiology. Renal physiology · 2018
    Article
  17. Article
  18. The Circadian Clock in the Regulation of Renal Rhythms.Journal of biological rhythms · 2015
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Jacob Richards1600 SW Archer Rd., Box 100224, Gainesville, FL 32610, USA. Michelle.Gumz@medicine.ufl.edu
Megan M Greenlee
Lauren A Jeffers
Kit-Yan Cheng
Laijing Guo
Douglas C Eaton
Michelle L Gumz
University of Florida · USEmory University · US

Funding

IRACDA Fellowships in Research and Science Training (FIRST)K12GM000680 · NIGMS · EMORY UNIVERSITY · PI BROWN, LOU ANN S, MCCARTY, NAEL A · 2000 to 2024
$41.2M
UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
REGULATION OF SODIUM IN TIGHT EPITHELIAR37DK037963 · NIDDK · EMORY UNIVERSITY · PI EATON, DOUGLAS C. · 2002 to 2011
$3.8M
PRE&POST-DOCTORAL TRAINING IN NEPHROLOGY&HYPERTENSIONT32DK007518 · NIDDK · UNIVERSITY OF FLORIDA · PI SEGAL, MARK S. · 1986 to 2011
$1.7M
A Functional Role for the Circadian Clock Protein Per1 in the Regulation of ??ENaK01DK085193 · NIDDK · UNIVERSITY OF FLORIDA · PI GUMZ, MICHELLE L · 2010 to 2014
$625k
NCATS NIH HHS UL1 TR000064NIDDK NIH HHS 5R37DK-037963-25NIDDK NIH HHS DK-085193NIDDK NIH HHS K01 DK085193NIDDK NIH HHS R37 DK037963NIDDK NIH HHS T32 DK-07518NIGMS NIH HHS 5K12GM-000680-12NIGMS NIH HHS K12 GM000680
6 · The paper itself

Abstract

Increasing evidence suggests that the circadian clock plays an important role in the control of renal function and blood pressure. We previously showed that the circadian clock protein Period (Per)1, positively regulates the expression of the rate limiting subunit of the renal epithelial sodium channel (αENaC), which contributes to blood pressure regulation. Casein kinases 1δ and 1ε (CK1δ/ε) are critical regulators of clock proteins. CK1δ/ε must phosphorylate the circadian clock protein Per1 in order for the latter to enter the nucleus. We used a commercially available CK1δ/ε inhibitor, PF670462, to test the effect of CK1δ/ε blockade and inhibited Per1 nuclear entry on αENaC in a model of the renal cortical collecting duct (mpkCCD(c14) cells). CK1δ/ε blockade prevented Per1 and Clock from interacting with an E-box from the αENaC promoter. CK1δ/ε inhibition reduced αENaC mRNA levels by <60%. A similar decrease in αENaC mRNA was observed following siRNA-mediated CK1δ/ε knock-down. Inhibition of CK1δ/ε effectively prevented the transcriptional response of αENaC to aldosterone, suggesting an interaction between the circadian clock and aldosterone-mediated regulation of αENaC. CK1δ/ε inhibition significantly reduced αENaC but increased Caveolin-1 membrane protein levels; transepithelial current, a measure of ENaC activity, was decreased. Importantly, single channel analysis in amphibian renal cells demonstrated a dramatic decrease in the number of patches with observable ENaC current following CK1δ/ε inhibition. The present study shows for the first time that CK1δ/ε inhibition and impaired Per1 nuclear entry results in decreased αENaC expression and ENaC activity, providing further support for direct control of ENaC by the circadian clock.

Indexed as

AnimalsCasein Kinase 1 epsilonCasein Kinase IdeltaCell LineCells, CulturedCLOCK ProteinsEpithelial Sodium ChannelsKidney Tubules, CollectingMicePeriod Circadian ProteinsPhosphorylationPyrimidinesCasein Kinase 1 epsilonCasein Kinase IdeltaClock protein, mouseCLOCK ProteinsEpithelial Sodium ChannelsPeriod Circadian ProteinsPF-670462Pyrimidines

Identifiers

PMID22832921
PMCPMC3469687
OpenAlexW2021296833

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.