Chronic kidney disease (CKD) is a growing public health epidemic that is associated with a markedly increased risk of cardiovascular mortality. Disordered mineral metabolism and particularly, disordered phosphorus metabolism appears to be a contributing factor. Fibroblast growth factor 23...

The molecular interactions of fibroblast growth factor 23 (FGF23), klotho and vitamin D coordinate to regulate the delicate phosphate levels of the body. Vitamin D can induce both FGF23 and klotho synthesis to influence renal phosphate balance. In the presence of klotho, FGF23 protein gains...

Klotho is an anti‑aging protein predominantly expressed in the kidney, parathyroid glands and choroid plexus of the brain. Klotho exists in two forms, a membrane form and a soluble secreted form. Recent studies show that the secreted Klotho possess sialidase activity and regulates several...

This chapter will review the various biological actions of the mouse fibroblast growth factor 15 (Fgf15) and human fibroblast growth factor 19 (FGF19). Unlike other members of the fibroblast growth factor (FGF) family, the Fgf15 and FGF19 orthologs do not share a high degree of sequence...

Bone is involved in the maintenance of phosphate and vitamin D homeostasis via its production and secretion of FGF23 and serves as a reservoir for the storage and release of calcium and phosphate into the circulation. Alterations in mineralization of extracellular matrix and the remodeling...

Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone‑parathyroid‑kidney axis, which is modulated by 1,25(OH)2‑vitamin D (1,25(OH)2D), dietary and circulating phosphate and possibly PTH. FGF23 was discovered as the humoral factor in tumors that causes...

The ability of the Fibroblast Growth Factor (FGF) 19 subfamily to signal in an endocrine fashion sets this subfamily apart from the remaining five FGF subfamilies known for their paracrine functions during embryonic development. Compared to the members of paracrine FGF subfamiles, the three...

Klotho and fibroblast growth factor 1 (FGFR1) are expressed not only in FGF23’s classical target organ, the kidney, but also in other organs such as the parathyroid. FGF23 acts on the parathyroid to decrease PTH mRNA and serum PTH levels. It does this by activating the MAPK pathway. In...

Fibroblast growth factor (FGF) 23 is a hormone that acts to decrease phosphate, 1,25‑dihydroxyvitamin D and parathyroid hormone levels in circulation. Particularly, appropriate actions of FGF23 are essential for maintaining physiological phosphate and vitamin D metabolism. Therefore, either...

The prevalence of obesity and diabetes has been dramatically increasing during the last decade suggesting a greater patient need for more efficacious and safer drugs. Large molecule therapy has played an important role in diabetes since the discovery of insulin. This legacy was continued upon...

Endocrine fibroblast growth factors (FGFs) have been recognized as hormones that regulate a variety of metabolic processes. FGF19 is secreted from intestine upon feeding and acts on liver to suppress bile acid synthesis. FGF21 is secreted from liver upon fasting and acts on adipose tissue to...

FGF19 differs from the classical FGFs in that it has a much‑reduced heparan sulfate proteoglycan binding affinity that allows it to act as endocrine hormone. Although FGF19 regulates several different metabolic activities, it still activates downstream signaling pathways through FGF...

Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane‑anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for...

Fibroblast growth factors (FGFs) and their cognate receptors, FGF receptors (FGFRs), play critical roles in a variety of normal developmental and physiological processes. Numerous reports support a role for deregulation of FGF‑FGFR signaling, whether it is at the ligand and/or receptor...