Claudin‐2 Confers Calcium Permeability to the Jejunum and Ileum in Early Life
Bibliographic record
Abstract
Infants and children must maintain a net positive calcium (Ca 2+ ) balance in order to achieve an optimal peak bone mineral density by early adulthood. Across the small intestine, Ca 2+ is absorbed via transcellular and paracellular pathways although the molecular details of these pathways in early life are not well delineated. Claudins are tight junction proteins that confer selective permeability to epithelia. Claudins‐2, −12 and −15 are expressed and have been implicated in paracellular Ca 2+ permeability across intestinal epithelia. To date, the functional contribution of these claudins to the Ca 2+ permeability (P Ca 2+ ) of small intestine segments has not been defined. The objective of this study was therefore to 1) determine if P Ca 2+ across small intestine segments changed with postnatal development 2) to asses whether claudin‐2 or −12 contribute P Ca 2+ to the small intestine. To this end, basolateral to apical 45 Ca 2+ fluxes on ex vivo intestinal segments in Ussing chambers were employed to indirectly assess permeability to Ca 2+ . We observed greater 45 Ca 2+ flux in P14 vs 2‐month mice across the duodenum (31.8 ± 2.2 vs 9.5 ± 2.0 nmol/h/cm 2 , P<0.0001) and jejunum (42.3 ± 3.9 vs 21.8 ± 3.5 nmol/h/cm 2 , P<0.01) but not ileum (40.5 ± 3.2 vs 30.1 ± 5.7 nmol/h/cm 2 , P=0.13). Next, we measured P Ca 2+ directly in Ussing chambers using diffusion potentials. P Ca 2+ was significantly greater in younger mice across the duodenum (1.43 ± 0.04 vs 1.13 ± 0.08 × 10 −4 cm/s, P<0.01), jejunum (1.64 ± 0.09 vs 0.84 ± 0.04 × 10 −4 cm/s, P<0.0001) and ileum (1.72 ± 0.08 vs 0.81 ± 0.05 × 10 −4 cm/s, P<0.0001). To determine if claudin‐2 or −12 facilitates greater P Ca 2+ at P14, diffusion potential experiments were repeated on Cldn2 or Cldn12 knockout (KO) mice. P Ca 2+ was decreased in Cldn2 KO mice at P14 across the jejunum (1.85 ± 0.09 vs 1.24 ± 0.07 × 10 −4 cm/s, P<0.0001) and ileum (1.92 ± 0.07 vs 1.09 ± 0.06 × 10 −4 cm/s, P<0.0001) to levels not different than 2‐month WT and KO mice. No differences were observed between Cldn12 knockout mice compared to wildtype littermates at either age. We conclude that the younger mice have enhanced Ca 2+ permeability along the small intestine relative to older animals. Further, the increased jejunal and ileal Ca 2+ permeability is mediated by claudin‐2 which likely contributes to a positive calcium balance for normal growth. Support or Funding Information This work was funded by grants from the Women and Children's Health Research Institute, which is supported by the Stollery Children's Hospital Foundation, and the National Sciences and Engineering Research Council to RTA, who is the Canada Research Chair in Renal Epithelial Transport Physiology. MRB is supported by a Vanier Canada Graduate Scholarship, and Alberta Innovates Clinician Fellowship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".