Evidence map›Paper›PMID 21937605›Full record

ArticleAmerican journal of physiology. Renal physiology2012

The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption.

Wanling Pan, Jelena Borovac, Zachary Spicer, Joost G Hoenderop, René J Bindels, Gary E Shull, Michael R Doschak, Emmanuelle Cordat, R Todd Alexander

Open access · greenAbstract 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 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

56 citing papers in PubMed, 100 citations in OpenAlex.

  1. Trial
  2. Article
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  5. Article
  6. Histamine regulates the activity and the expression of the NaInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  7. Calcium-Sensing Receptor in the Thick Ascending Limb and Renal Response to Hypercalcemia.Journal of the American Society of Nephrology : JASN · 2025
    Article
  8. Article
  9. Biology of calcium homeostasis regulation in intestine and kidney.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  10. Article
  11. Article
  12. Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024
    Review
  13. Hypomagnesemia in Post Thyroidectomy Patient: An Underestimated Entity.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023
    Article
  14. Molecular mechanisms altering tubular calcium reabsorption.Pediatric nephrology (Berlin, Germany) · 2022
    Review
  15. Article
  16. Article
  17. Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Wanling PanDivision of Nephrology, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Jelena Borovac
Zachary Spicer
Joost G Hoenderop
René J Bindels
Gary E Shull
Michael R Doschak
Emmanuelle Cordat
R Todd Alexander
University of Cincinnati · USRadboud University Nijmegen · NLUniversity of Alberta · CA

Funding

MODELS FOR GENETIC DISORDERS OF ACID-BASE TRANSPORTR37DK050594 · NIDDK · UNIVERSITY OF CINCINNATI · PI SHULL, GARY EDWARD · 2000 to 2009
$6.0M
MODELS FOR GENETIC DISORDERS OF ACID BASE TRANSPORTR01DK050594 · NIDDK · UNIVERSITY OF CINCINNATI · PI SHULL, GARY EDWARD · 1996 to 2013
$1.9M
CIHR 106565-1NIDDK NIH HHS DK050594
6 · The paper itself

Abstract

Passive paracellular proximal tubular (PT) and intestinal calcium (Ca(2+)) fluxes have been linked to active sodium (re)absorption. Although the epithelial sodium/proton exchanger, NHE3, mediates apical sodium entry at both these sites, its role in Ca(2+) homeostasis remains unclear. We, therefore, set out to determine whether NHE3 is necessary for Ca(2+) (re)absorption from these epithelia by comparing Ca(2+) handling between wild-type and NHE3(-/-) mice. Serum Ca(2+) and plasma parathyroid hormone levels were not different between groups. However, NHE3(-/-) mice had increased serum 1,25-dihydroxyvitamin D(3). The fractional excretion of Ca(2+) was also elevated in NHE3(-/-) mice. Paracellular Ca(2+) flux across confluent monolayers of a PT cell culture model was increased by an osmotic gradient equivalent to that generated by NHE3 across the PT in vivo and by overexpression of NHE3.( 45)Ca(2+) uptake after oral gavage and flux studies in Ussing chambers across duodenum of wild-type and NHE3(-/-) mice confirmed decreased Ca(2+) absorption in NHE3(-/-) mice compared with wild-type mice. Consistent with this, intestinal calbindin-D(9K), claudin-2, and claudin-15 mRNA expression was decreased. Microcomputed tomography analysis revealed a perturbation in bone mineralization. NHE3(-/-) mice had both decreased cortical bone mineral density and trabecular bone mass. Our results demonstrate significant alterations of Ca(2+) homeostasis in NHE3(-/-) mice and provide a molecular link between Na(+) and Ca(2+) (re)absorption.

Indexed as

AnimalsBone DensityCalbindinsCalcitriolCalciumCell LineClaudinsDuodenumIntestinal AbsorptionKidneyMiceMice, KnockoutOpossumsParathyroid HormoneS100 Calcium Binding Protein GSodium-Hydrogen Exchanger 3CalbindinsCalcitriolCalciumclaudin 15ClaudinsCldn2 protein, mouseParathyroid HormoneS100 Calcium Binding Protein GSlc9a3 protein, mouseSodium-Hydrogen Exchanger 3Sodium-Hydrogen Exchangers

Identifiers

PMID21937605
PMCPMC3330715
OpenAlexW2109355990

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.