Why does FGF23 increase in CKD?
In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone.
Does FGF23 inhibit vitamin D?
FGF23 plays a central role in vitamin D metabolism: It inhibits calcitriol synthesis in the kidney and stimulates the catabolism of active vitamin D sterols. In turn, calcitriol stimulates FGF23 and Klotho expression.
What is the role of fibroblast growth factor 23 FGF23 in calcium regulation?
FGF-23 also is a regulator of PTH. FGF-23 inhibits parathyroid function and increases the parathyroid expression of the CaSR and vitamin D receptor making the gland more sensitive to the inhibitory actions of calcium and calcitriol. Whether FGF-23 is regulated by dietary phosphate is unclear.
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).
What is a normal FGF23 level?
In normal controls, the median FGF23 level was 13 RU/ml and ranged from 5 to 210 RU/ml (Table 1), in a pattern that was not normally distributed (Fig. 1).
What is the function of FGF23?
Does FGF23 increase calcium?
Moreover, FGF23 has several additional physiological functions, which include inhibition of renal phosphate reabsorption, increased conservation of calcium and sodium in the kidney, support of a normal responsiveness of the kidney to PTH, and regulation of bone mineralization.
What causes low FGF23?
FGF23 mutations are postulated to cause the susceptibility by changing protein structure of FGF23. A homozygous mutation of Klotho has been shown to make the expression of Klotho protein to be markedly reduced, resulting in diminished ability of FGF23 protein to act on target organs [38].
What causes increase of FGF23?
High level of FGF23 is also found in patients with chronic kidney disease, especially in patients with end-stage renal disease [40]. The high level of FGF23 in these diseases is regarded as a compensatory response to hyperphosphatemia or phosphate overload.
What does FGF23 do to bone?
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).
What triggers FGF23?
Promoter activation by 1,25(OH)2D
1,25(OH)2D is the most important systemic factor regulating FGF23. The administration of 1,25(OH)2D increases FGF23 levels, while the disruption of 1,25(OH)2D pathways reduces circulating FGF23 in mice (117, 166).
What organ is the target of action for FGF23?
Dietary phosphate intake stimulates the production and secretion of FGF23 from osteocytes, and FGF23 directly targets the kidney to increase phosphate excretion by downregulating the cell surface expression of the sodium-dependent phosphate transporters, NaPi-2a and NaPi-2c, in the proximal tubule (10–14) (Figure
What causes release of FGF23?
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.
What stimulates 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.