Intestinal epithelial ablation of Pit‐2/Slc20a2 in mice leads to sustained elevation of vitamin D3upon dietary restriction of phosphate
| Autor: | Nadège Poncet, Carsten A. Wagner, Udo Schnitzbauer, Nati Hernando, Eva María Pastor-Arroyo, Thomas Knöpfel, Jürg Biber, Pedro Henrique Imenez Silva |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vitamin medicine.medical_specialty Physiology Ileum 030204 cardiovascular system & hematology Apical membrane Phosphate Intestinal absorption 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Endocrinology chemistry Internal medicine medicine Large intestine Cotransporter Hormone |
| Zdroj: | Acta Physiologica. 230 |
| ISSN: | 1748-1716 1748-1708 |
| DOI: | 10.1111/apha.13526 |
| Popis: | AIM Several Na$^{+}$ -dependent phosphate cotransporters namely NaPi-IIb/SLC34A3, Pit-1/SLC20A1 and Pit-2/SLC20A2, are expressed at the apical membrane of enterocytes but their contribution to active absorption of phosphate is unclear. The aim of this study was to compare their pattern of mRNA expression along the small and large intestine and to analyse the effect of intestinal depletion of Pit-2 on phosphate homeostasis. METHODS Intestinal epithelial Pit-2 deficient mice were generated by crossing floxed Pit-2 with villin-Cre mice. Mice were fed two weeks standard or low phosphate diets. Stool, urine, plasma and intestinal and renal tissue were collected. Concentration of electrolytes and hormones, expression of mRNAs and proteins and intestinal transport of tracers were analysed. RESULTS Intestinal mRNA expression of NaPi-IIb and Pit-1 is segment-specific whereas the abundance of Pit-2 mRNA is comparable along the whole intestine. In ileum, NaPi-IIb mRNA expression is restricted to enterocytes whereas Pit-2 mRNA is found in epithelial and non-epithelial cells. Overall, their mRNA is not regulated by dietary phosphate. The absence of Pit-2 from intestinal epithelial cells does not affect systemic phosphate-homeostasis under normal dietary conditions. However, in response to dietary phosphate restriction, Pit-2 deficient mice showed exacerbated hypercalciuria and sustained elevation of 1,25(OH)$_{2}$ vitamin D$_{3}$ . CONCLUSIONS In mice, the intestinal Na$^{+}$ /phosphate cotransporters are not coexpressed in all segments. NaPi-IIb but not Pit-2 mRNA is restricted to epithelial cells. Intestinal epithelial Pit-2 does not contribute significantly to absorption of phosphate under normal dietary conditions. However, it may play a more significant role upon dietary phosphate restriction. |
| Databáze: | OpenAIRE |
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