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.
|Title of host publication||Phosphates|
|Subtitle of host publication||Sources, Properties and Applications|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||14|
|Publication status||Published - 01-12-2012|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)