Role of phosphate transporter in skeletal and extraskeletal calcification

Atsushi Suzuki, Sahoko Sekiguchi-Ueda, Megumi Shibata, Shogo Asano, Mitsuyasu Itoh

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

It is well known that phosphate (Pi) deprivation is associated with hypophosphatemia and tissue damage. Plasma Pi level is determined by the co-transport of Na and Pi across renal epithelial cells. It is, however, less clear how cytoplasmic Pi is regulated towards enhanced extracellular Pi concentration. The type-III Pi transporter Pit-1 was previously found to be preferentially expressed in developing long bones. At the same time, Pit-1 is expressed in ubiquitous tissues including vascular smooth muscle cells (VSMC) and soft tissues, suggesting its possible role in ectopic calcification. In fact, recent studies revealed that elevated Pi concentrations in extracellular milieu drives VSMC to osteochondrogenic phenotype change and calcification through Pit-1. To gain insight into the in vivo function of Pit-1, we constructed a Pit-1 transgenic (Tg) rat model. Pit-1 Tg rats showed normal bone development in youth, but decreased their bone mass according to aging. At the same time, Pit-1 Tg rats showed spontaneous cataract, overt proteinuria due to podocyte injury in their kidney. On the contrary, Pit-1 Tg rats did not show apparent ectopic calcification. These results suggest that Pi overload damages many tissues and organs, and that the counter-regulatory system against Pi overload protects ectopic calcification.

Original languageEnglish
Title of host publicationPhosphates
Subtitle of host publicationSources, Properties and Applications
PublisherNova Science Publishers, Inc.
Pages217-230
Number of pages14
ISBN (Print)9781619421233
Publication statusPublished - 01-12-2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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