FGF23 - Fibroblast Growth Factor 23 | Elisa - Clia - Antibody - Protein

Background:

Fibroblast Growth Factor 23, or FGF23, is a hormone primarily known for its role in phosphate and vitamin D metabolis by reducing the reabsorption of phosphate in the kidneys, leading to increased urinary excretion of phosphate. FGF23 also affects vitamin D metabolism. It inhibits the production of activated vitamin D (calcitriol) in the kidneys, which is important for calcium absorption. FGF23 is mainly produced by osteocytes, which are cells found in bone tissue. Osteocytes are sensitive to changes in phosphate levels and produce FGF23 in response to high phosphate or vitamin D levels. FGF23 production is regulated by various factors, including phosphate intake, dietary vitamin D, parathyroid hormone (PTH), and the calcium-sensing receptor. Elevated levels of FGF23 are associated with hypophosphatemia (low phosphate levels) due to increased urinary excretion of phosphate.Conditions such as chronic kidney disease (CKD) can lead to elevated FGF23 levels as the kidneys are less able to excrete phosphate efficiently. Some rare genetic disorders, like X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR), are characterized by increased FGF23 levels, leading to phosphate wasting and bone abnormalities.

Protein Structure:

FGF23 is a 251-amino acid protein that undergoes post-translational modifications, including glycosylation and proteolytic cleavage. Its structure includes:

• N-terminal signal peptide: Directs the protein for secretion.
• FGF core domain: Characteristic of the FGF family, involved in receptor binding.
• C-terminal tail: Essential for its biological activity and interaction with receptors.

FGF23 differs from other FGFs due to its specific role in mineral metabolism rather than broader developmental processes.

Classification and Subtypes:

FGF23 belongs to the FGF19 subfamily, which includes FGF19 and FGF21. These endocrine FGFs function as hormones circulating in the bloodstream to exert effects on distant organs.

Function and Biological Significance:

• Phosphate Homeostasis: FGF23 reduces serum phosphate levels by decreasing renal phosphate reabsorption and reducing intestinal phosphate absorption through the suppression of vitamin D activation.
• Vitamin D Metabolism: It inhibits the enzyme 1α-hydroxylase in the kidneys, reducing the conversion of 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D.
• Bone Mineralization: By regulating phosphate and vitamin D levels, FGF23 indirectly influences bone mineralization processes.

Interactions:

• FGFRs and α-Klotho: FGF23 signals through fibroblast growth factor receptors (FGFR1c, FGFR3c, and FGFR4) in the presence of the co-receptor α-Klotho. This interaction is crucial for its activity in regulating phosphate and vitamin D metabolism.
• Parathyroid Hormone (PTH): FGF23 interacts with PTH, another key regulator of calcium and phosphate homeostasis. FGF23 can inhibit PTH secretion, creating a feedback loop that maintains mineral balance.

Clinical Issues:

• Hypophosphatemic Disorders: Elevated levels of FGF23 cause conditions such as X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR), characterized by low serum phosphate and defective bone mineralization.
• Chronic Kidney Disease (CKD): In CKD, FGF23 levels rise as a compensatory response to maintain phosphate balance, but this can lead to adverse effects such as left ventricular hypertrophy and increased cardiovascular risk.
• Tumor-Induced Osteomalacia (TIO): Some tumors produce excess FGF23, leading to hypophosphatemia and osteomalacia.

Summary:

FGF23 is a crucial endocrine regulator of phosphate and vitamin D metabolism. It acts on the kidneys to reduce phosphate reabsorption and inhibit vitamin D activation, thereby maintaining phosphate homeostasis. Through its interactions with FGFRs and α-Klotho, FGF23 exerts significant effects on bone health and mineral metabolism. Dysregulation of FGF23 is implicated in various clinical conditions, including hypophosphatemic disorders and chronic kidney disease, highlighting its importance in both health and disease. Further research continues to explore its mechanisms and potential therapeutic applications