Fibroblast growth factor 23 (FGF23) contributes to regulation of hepcidin/ferroportin axis

Abstract

Fibroblast growth factor 23 (FGF23) is a recently discovered regulator of phosphate and mineral metabolism and has been associated with both the progression of chronic kidney disease (CKD) and mortality in dialysis patients. Serum levels of FGF23 are extremely elevated, as high as > 1 ng/mL in patients with hemodialysis (HD) but the mechanisms are poorly understood. Here, to confirm the direct implication of FGF23 in iron homeostasis, we examined the mRNA expression of hepcidin, ferroportin, and hypoxia Inducible Factors (HIFs) in HepG2 cells. Serum treatment of patients with HD resulted in an up-regulation of hepcidin expression and a down-regulation of ferroportin in HepG2 cells. A significant down-regulation of ferroportin and HIFs was observed in HepG2 cells after FGF23 treatment. Conversely, hepcidin was regulated by FGF23 in a dose- and time-dependent manner. Low concentrations of FGF23 increased hepcidin expression, and high concentrations of FGF23 revealed a change-over to down-regulation of hepcidin expression. Both hepcidin and ferroportin are well known to be the main regulators in iron homeostasis. This study, thus, demonstrated that the FGF23 implicated directly in iron homeostasis as a clinical concentrate iron is compatible with serum levels in long-term patients with HD.