NaPiIIb Expression and Intestinal Phosphate Absorption are Increased in Young Mice

• Author / Creator

  MacDonald, Tate

• Phosphate is important for a variety of physiological functions, including the composition of bone via formation of the calcium-phosphate salt hydroxyapatite. Given that bone mineralization occurs very rapidly early in life, young mammals require high phosphate absorption to establish and maintain the required phosphate balance for the high rate of bone mineralization. Absorption of all ions including phosphate from the small intestine takes place via either the active transcellular or passive paracellular pathway. A key player in the former pathway is NaPiIIb; a secondary active sodium-phosphate transporter expressed at the apical membrane of enterocytes. Conversely, claudins are a family of proteins expressed in the tight junction that govern the paracellular passage of specific ions. Failure to establish adequate phosphate balance often results in diminished bone integrity. This work sought to establish the relative importance of the two pathways of ion absorption in the upregulation of phosphate absorption in young animals. To accomplish this, ontogenic changes in expression of genes involved transcellular and paracellular phosphate absorption in mice were assessed between one day and six months of age. Additionally, functional differences in phosphate absorption via the two pathways of absorption were assessed in pre-weaning juvenile mice and adult mice. NaPiIIb message levels were consistently elevated along the length of the small intestine in juvenile mice. Accordingly, net transcellular phosphate flux assessed ex vivo was increased in juvenile mice relative to adult counterparts. NaPiIIb was specifically implicated in this increase by administering the NaPiIIb inhibitor NTX-1942 which attenuated the increased apical-to- basolateral phosphate absorption observed in young mice. Further, the expression of two claudins hypothesized to be involved in paracellular phosphate absorption; claudins -4 and -23; were upregulated early in murine development. Consistent with this, paracellular phosphate permeability was increased along the length of the small intestine in young mice relative to adults. The findings of this study are consistent with young mice increasing phosphate absorption via both the transcellular and paracellular pathway to the end of establishing a sufficiently high phosphate balance for normal bone mineralization.

• Subjects / Keywords

  • Phosphate
  • Absorption
  • Development
  • Transcellular
  • Paracellular
  • Claudin
  • Bone
  • Kidney
  • Small Intestine

• Graduation date

  Fall 2022

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-b5hd-9h08

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.