The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight
Abstract
Phosphate homeostasis is essential for health and is achieved via interaction between the
bone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphate
transporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disorders
are associated with disruption in these processes and can lead to significant morbidity and mortality.
The role of the kidney in phosphate homeostasis is well known, although it is recognized that the
cellular mechanisms in murine models and humans are different. Intestinal phosphate transport
also appears to differ in humans and rodents, with recent studies demonstrating a dominant role for
the paracellular pathway. The existence of phosphate sensing has been acknowledged for decades;
however, the underlying molecular mechanisms are poorly understood. At least three phosphate
sensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast Growth
Factor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormone
secretion in response to extracellular phosphate. All three of the proposed sensors are expressed
in the kidney and intestine but their exact function in these organs is unknown. Understanding
organ interactions and the mechanisms involved in phosphate sensing requires significant research
to develop novel approaches for the treatment of phosphate homeostasis disorders.
Origin | Publisher files allowed on an open archive |
---|---|
Licence |