Recent Advances in Fibro-blast Growth Factor-23 Functions

Shahzad Shoukat Nayani and Zhousheng Xiao*

Recent Advances in Fibro-blast Growth Factor-23 Functions

During the past decade a lot of work has been done to better understand the roles
of fibroblast growth factor-23; a relatively newly discovered endocrine hormone,
in multiple organ systems in the body.

This review focuses on expressions of FGF-23, co expressions of α-Klotho and FGF receptors,
and FGF-23 mediated end-organ effects in the physiological and pathological conditions.

We also discuss the controversial reports regarding α-Klotho-dependent and α-Klotho-independent
functions of FGF-23.

FGF-23 is a family member of 22 fibroblast growth factors including FGF-1-
FGF-23, all of which are not only structurally but also evolutionarily related proteins.

These FGFs have been classified as being paracrine, endocrine, or intracrine and using
a mammalian model the endocrine FGFs, especially FGF-23 an approximately 32 kD protein,
have been thoroughly investigated in recent years.

Local factors derived from bone itself also regulate its expression as seen
in cases of inactivating mutations of PHEX which results in
increased transcription and circulating levels of FGF-23.

α-Klotho is a unique molecule that establishes a regulatory system of calcium homeostasis
by affecting transepithelial transport of calcium, parathyroid hormone secretion,
and FGF-23 signal transduction.

Evolutionarily the FGF-23-α-Klotho system is part of a major milestone in
vertebrate evolution that started in the ocean when the early piscine ancestors
acquired the bony endoskeleton.

α-Klotho has been demonstrated to enhance FGF-23 activity over 10-fold11 and has also
been identified as a necessary co-receptor for FGF-23 binding due
to the phenotypic similarity observed in α-Klotho and FGF-23 knockout mice,
i.e.; hyperphosphatemia and hypercalcemia.

Nephrol Open J. 2016; 1(3): 51-58. doi: 10.17140/NPOJ-1-110