Emerging concepts on the FGF23 regulation and activity.

Area of Science:

• Endocrinology
• Mineral Metabolism
• Molecular Biology

Background:

• Fibroblast growth factor 23 (FGF23) is a hormone crucial for phosphate and calcium homeostasis.
• Secreted by bone cells, FGF23 primarily acts on the kidneys and parathyroid glands.

Purpose of the Study:

• To review current knowledge on FGF23 synthesis regulation.
• To explore FGF23's canonical and non-canonical signaling pathways.
• To discuss FGF23's role in various diseases and emerging anti-FGF23 therapies.

Main Methods:

• Narrative review of PubMed literature from 2000-2023.
• Keywords included FGF23 synthesis regulators, receptors, pathways, pathophysiology, and therapy.
• Focus on molecular mechanisms.

Main Results:

• FGF23 synthesis is complex, influenced by local and systemic factors, particularly bone mineralization.
• Excessive FGF23 is linked to congenital diseases, chronic kidney disease (CKD), and tumor-induced osteomalacia (TIO).
• Anti-FGF23 therapy shows promise for X-linked hypophosphatemia and TIO, but CKD management remains challenging.

Conclusions:

• Understanding FGF23's biochemistry and pathophysiology offers therapeutic targets for conditions with high FGF23 levels.
• Further research is needed to optimize anti-FGF23 strategies, especially in CKD.
• FGF23 modulation holds potential for treating diverse mineral metabolism disorders.