Fibroblast Growth Factor 23 (FGF23)

Fibroblast Growth Factor 23 (FGF23) is a secreted protein primarily produced by osteoblasts and osteocytes in bone. It plays a crucial role in phosphate and vitamin D homeostasis by suppressing renal phosphate reabsorption and inhibiting the synthesis of active vitamin D. FGF23 binds to fibroblast growth factor receptors (FGFRs) in target tissues, requiring αKlotho as a co-receptor for high-affinity binding in the kidneys. Dysregulation of FGF23 is implicated in various disorders, including autosomal dominant hypophosphatemic rickets, tumor-induced osteomalacia, and chronic kidney disease-mineral bone disorder.

FGF23 binds to FGFRs, primarily FGFR1c, in target tissues with αKlotho as a co-receptor, leading to downstream signaling involving ERK1/2 activation and SGK1-mediated phosphorylation events that regulate transporter abundance on cell membranes. This results in decreased renal phosphate reabsorption, decreased vitamin D synthesis, and increased calcium/sodium reabsorption.