The epithelial sodium/proton exchanger, NHE3, is necessary for renal and intestinal calcium (re)absorption
Why this work is in the frame
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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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it