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Publication : Intestinal epithelial ablation of Pit-2/Slc20a2 in mice leads to sustained elevation of vitamin D<sub>3</sub> upon dietary restriction of phosphate.

First Author  Pastor-Arroyo EM Year  2020
Journal  Acta Physiol (Oxf) Volume  230
Issue  2 Pages  e13526
PubMed ID  32564464 Mgi Jnum  J:302962
Mgi Id  MGI:6510976 Doi  10.1111/apha.13526
Citation  Pastor-Arroyo EM, et al. (2020) Intestinal epithelial ablation of Pit-2/Slc20a2 in mice leads to sustained elevation of vitamin D3 upon dietary restriction of phosphate. Acta Physiol (Oxf) 230(2):e13526
abstractText  AIM: Several Na(+) -dependent phosphate cotransporters, namely NaPi-IIb/SLC34A2, 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 2 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 more homogeneous. 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 expression 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 D3 . 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.
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