Claudin‐2 Confers Calcium Permeability to the Jejunum and Ileum in Early Life
Notice bibliographique
Résumé
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 .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».