What is the role of FGF23?

Normal Function The FGF23 gene provides instructions for making a protein called fibroblast growth factor 23, which is produced in bone cells. This protein is necessary in regulating the phosphate levels within the body (phosphate homeostasis).

Does calcitriol stimulate FGF23?

Fibroblast growth factor 23 (FGF23) is a circulating hormone that is synthesized by osteocytes and osteoblasts. In turn, calcitriol stimulates FGF23 and Klotho expression. In chronic kidney diseases, FGF23 concentration increases as GFR declines, whereas Klotho tissue expression decreases.

Does fibroblast growth factor 23 increase bone growth?

Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease (CKD) and may play a critical role in mineral ion disorders and bone metabolism in these patients.

What stimulates FGF23?

Recently, it has been shown that leptin, a hormone secreted by white adipose tissue that acts centrally on hypothalamus and peripherally on other organs to control energy intake, expenditure, and bone homeostasis, stimulates FGF23 production in bone (205).

What causes FGF23 release?

FGF23 is secreted by osteocytes in response to increased calcitriol. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule. Thus, FGF23 decreases the reabsorption of calcium and increases excretion of phosphate.

What stimulates the release of calcitriol?

Parathyroid hormone stimulates calcitriol production in the kidney by increasing the synthesis of 1-α hydroxylase. Calcitriol has several important functions in the body. It maintains serum calcium levels by increasing calcium absorption in the gastrointestinal tract.

Does vitamin D increase phosphate absorption?

Vitamin D functions by stimulating intestinal calcium and phosphorus absorption, by stimulating bone calcium mobilization, and by increasing renal reabsorption of calcium in the distal tubule.

What causes too much fibroblast growth factor 23?

It is currently believed that the excessive osteocytic and osteoblastic FGF23 secretion in both diseases is either driven by the impaired mineralization of the extracellular matrix, which may be detected by matrix-embedded bone cells through a putative sensing mechanism that may involve FGF receptors (19, 20), or by an …

What triggers FGF23?

The expression of FGF23 is regulated by both VDR-dependent and VDR-independent signaling. Stimulation of the 1,25(OH)2D-VDR pathway induces the expression of FGF23, as evidenced by increased FGF23 levels after 1,25(OH)2D administration.

What is the function of FGF23?

Fibroblast growth factor 23 (FGF23) was identified as the last member of FGF family. FGF23 is produced by bone and reduces serum phosphate level by suppressing phosphate reabsorption in proximal tubules and intestinal phosphate absorption through lowering 1,25-dihydroxyvitamin D level.

How many amino acids are in the FGF23 protein?

FGF23 is produced as a peptide with 251 amino acids. There is a signal peptide with 24 amino acids, and the secreted FGF23 protein consists of 227 amino acids. A part of FGF23 protein is proteolytically cleaved between 179Arg…

What is the pathophysiology of FGF23 deficiency?

Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets. Mice lacking either FGF23 or the klotho enzyme display premature aging due to hyperphosphatemia.

Does phosphate increase FGF23?

Conversely, 1,25(OH)2D was shown to increase FGF23 level and enhance promoter activity of FGF23gene [7]. It has been also shown that high phosphate diet increases circulatory FGF23 [8]. However, acute changes of serum phosphate do not alter FGF23 levels in human [9].