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REVIEW

FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player?

Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts and Department of Pathology, Nagasaki University School of Biomedical Science, Nagasaki, Japan

Submitted 3 September 2008 ; accepted in final form 14 November 2008

ABSTRACT

Understanding the physiological regulation of mineral ion metabolism is essential for determining the pathomechanisms of skeletal, vascular, and renal diseases associated with an abnormal regulation of calcium and phosphate homeostasis. Normal calcium and phosphate balance is delicately maintained by endocrine factors that coordinate to influence the functions of the intestine, bone, parathyroid gland, and kidney. Under physiological conditions, the kidneys play an important role in maintaining normal mineral ion balance by fine-tuning the amount of urinary excretion of calcium and phosphate according to the body's needs. Fibroblast growth factor (FGF)23 regulates urinary phosphate excretion to maintain systemic phosphate homeostasis. The exact mode of action of the phosphaturic effects of FGF23 is not fully understood and is an intense area of research. Studies suggest, however, that FGF23, by interacting with FGF receptors, can initiate downstream signaling events and that Klotho, a transmembrane protein, facilitates the interaction of FGF23 with its receptor. FGF23 can inhibit the activities of 1--hydroxylase and sodium-phosphate cotransporter in the kidney to influence the overall systemic phosphate balance. This article briefly summarizes how FGF23 might coordinately regulate systemic phosphate homeostasis and how Klotho is involved in such regulation.

vitamin D; mineral metabolism; kidney; calcification

This article has been cited by other articles:

				T. Nakatani, M. Ohnishi, and M. S. Razzaque Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic (Hyp) mouse model FASEB J, November 1, 2009; 23(11): 3702 - 3711. [Abstract] [Full Text] [PDF]