Fibroblast growth factor 23

Fibroblast growth factor 23 (FGF-23) is a hormone (32kDa) belonging to the FGF-19 subfamily. Its main function is to regulate mineral homeostasis, specifically phosphate reabsorption and inhibition of the enzyme to form activated vitamin D. FGF-23 is produced primarily by osteocytes and osteoblasts. However, under pathologic conditions, such as chronic inflammation, macrophages and other tissues (e.g. tumors) can also be sources of FGF-23. Signaling of FGF-23 occurs via the FGF receptors (FGFR), with or without klotho as the co-receptor. Interestingly, FGF-23 can be cleaved by pro-protein convertases into 2 separate fragments, effectively separating the binding sites for FGFRs and klotho. Overproduction of FGF-23 can cause rickets or osteomalacia and elevated levels have been correlated with adverse clinical outcomes in chronic kidney, cardiovascular, inflammatory bowel, and infectious diseases. These adverse clinical outcomes are most likely due to uncontrolled inflammation. The link between FGF-23 and inflammation is partly due to its effect on the generation of active vitamin D, which downregulates inflammatory mediators, such as IL-6, IL-12, IL-23, TNFa, IFN?, CRP, and fibrinogen. In addition, FGF-23 production can be induced by vitamin D and a variety of immune mediators: TGF-?2, TNFa, and NF?b. The constant high levels of FGF-23 in chronic kidney disease can lead to cardiovascular disease and infections, both leading causes of mortality in these patients. Independent of kidney disease and circulating mineral levels, elevated FGF-23 is associated with left ventricular hypertrophy, cardiac fibrosis, increased hypertension, and subclinical atherosclerosis, which may be due to its regulation of ACE2 expression and infiltration of inflammatory macrophages.

Swiss-Prot Accession Number: Q9GZV9