Recombinant Human FGF-23 Protein

Fibroblast growth factor 23 (FGF‑23) is a 30‑32 kDa member of the FGF family, within a subfamily that also includes FGF‑19 and FGF‑21. FGF proteins contain a 120 amino acid (aa) core FGF domain that exhibits a beta ‑trefoil structure (1, 2). FGF‑19 subfamily members are highly diffusible molecules owing to their poor ECM/heparin sulfate binding and plasma‑stabilizing intramolecular folds (2‑4). Mature human FGF‑23 contains an atypical (very low affinity) heparin binding site (aa 134‑162), a proteolytic cleavage site (Arg179‑Ser180), and multiple O‑linked glycosylation sites with Thr178 being of particular importance (4‑7). O‑linked glycosylation at Thr178 blocks the cleavage of FGF‑23, thereby preventing loss of FGF‑23 activity (7, 8). Mature human FGF‑23 shows 72% aa identity to mouse FGF‑23 and is active on mouse cells (6). FGF‑23 exerts its effects through a ternary complex that includes Klotho and an FGF receptor (FGF R4 or the "c" isoforms of FGF R1 or FGF R3). Klotho has a restricted distribution that limits FGF‑23 activity (9‑11). FGF‑23 is produced by osteocytes and osteoblasts in response to high circulating phosphate levels, elevated parathyroid hormone, and circulatory volume loading. It functions as an endocrine phosphatonin by suppressing circulating phosphate levels (12). FGF‑23 interaction with renal proximal tubular epithelium decreases the renal resorption of phosphate by down‑regulating phosphate transporters and by suppressing vitamin D production. It also decreases the intestinal absorption of phosphate (13).