The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".