Increased Slc34a2 expression and paracellular phosphate permeability contribute to high intestinal phosphate absorption in young mice.

AIM: Phosphorus is a critical constituent of bone as a component of hydroxyapatite. Bone mineral content accrues rapidly early in life necessitating a positive phosphorus balance, which could be established by a combination of increased renal reabsorption and intestinal absorption. Intestinal absorption can occur via a transcellular pathway mediated by the apical sodium-phosphate cotransporter, Slc34a2/NaPiIIb or via the paracellular pathway. We sought to determine how young mammals increase dietary phosphorus absorption from the small intestine to establish a positive phosphorus balance, a prerequisite for rapid bone growth. METHODS: The developmental expression profile of genes mediating phosphate absorption from the small intestine was determined in mice by qPCR and immunohistochemistry. Additionally, Ussing chamber studies were performed on small bowel of young (p7-p14) and older (8- to 17-week-old) mice to examine developmental changes in paracellular Pi permeability and transcellular Pi transport. RESULTS: Blood and urinary Pi levels were higher in young mice. Intestinal paracellular phosphate permeability of young mice was significantly increased relative to older mice across all intestinal segments. NaPiIIb expression was markedly increased in juvenile mice, in comparison to adult animals. Consistent with this, young mice had increased transcellular phosphate flux across the jejunum and ileum relative to older animals. Moreover, transcellular phosphate transport was attenuated by the NaPiIIb inhibitor NTX1942 in the jejunum and ileum of young mice. CONCLUSION: Our results are consistent with young mice increasing phosphate absorption via increasing paracellular permeability and the NaPiIIb-mediated transcellular pathway.

Developmental Changes in Phosphate Homeostasis.

Phosphate is a multivalent ion critical for a variety of physiological functions including bone formation, which occurs rapidly in the developing infant. In order to ensure maximal bone mineralization, young animals must maintain a positive phosphate balance. To accomplish this, intestinal absorption and renal phosphate reabsorption are greater in suckling and young animals relative to adults. This review discusses the known intestinal and renal adaptations that occur in young animals in order to achieve a positive phosphate balance. Additionally, we discuss the ontogenic changes in phosphotropic endocrine signalling as it pertains to intestinal and renal phosphate handling, including several endocrine factors not always considered in the traditional dogma of phosphotropic endocrine signalling, such as growth hormone, triiodothyronine, and glucocorticoids. Finally, a proposed model of how these factors may contribute to achieving a positive phosphate balance during development is proposed.