How does FGF23 affect phosphate?

FGF23 inhibits renal tubular reabsorption of phosphate through mechanisms independent of PTH as well as reduces circulating 1, 25(OH)2D through its dual effects to suppress Cyp27b1 production and to stimulate Cyp24 catabolism of 1,25(OH)2D.

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.

What causes high 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.

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.

Does FGF23 increase or decrease phosphate?

FGF23 targets the parathyroid gland to decrease PTH secretion and the kidney to increase urinary phosphorus excretion and to suppress synthesis of 1,25-dihydroxyvitamin D by decreasing renal tubular 1α-hydroxylase expression.

Does FGF23 increase phosphate?

As mentioned above, FGF23 promotes renal phosphate excretion by inhibiting cellular phosphate re-uptake from the urine in proximal renal tubules (Figure 1).

What is the function of FGF23?

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).

Is FGF23 high in CKD?

FGF23 is produced mainly by the bone [10, 11] and binds to Klotho-FGF receptor (FGFR) complex [12, 13]. Serum FGF23 level is high in patients of CKD, suggesting that FGF23 has some role in the development of CKD-MBD [14].

What does FGF23 stand for?

Fibroblast growth factor-23
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney.

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 does FGF23 do to bone?

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 stimulates FGF23 release?

FGF23 release is further stimulated by 1,25(OH)2D3 or activation of the vitamin D receptor (VDR), a negative feedback loop contributing to the limitation of 1,25(OH)2D3 formation [1].

What stimulates FGF23 secretion?

Which is an effect of FGF23 in mineral metabolism?

FGF23 is a 32-kDa (251 amino acid) protein produced by osteocytes and osteoblasts which makes the bone an endocrine organ that communicates with other organs involved in mineral homeostasis. FGF23 acts on its receptor complex, klotho-FGFR1, in the kidney to cause phosphaturia and to decrease calcitriol synthesis.

What is FGF23 blood test?

Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate homeostasis. FGF23 measurements are useful in the differential diagnosis of hypophosphatemic diseases. Intact FGF23 is elevated in patients with tumor induced osteomalacia (TIO) or X-linked hypophosphatemia (XLH).

Is FGF23 a hormone?

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney.

What activates 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 1).

What is serum FGF23?

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by osteocytes and osteoblasts, and high serum FGF23 levels are a significant risk factor for patients with chronic kidney disease (CKD) [1, 2].

What happens in hyperphosphatemia?

When you have hyperphosphatemia, the phosphate levels in your body become very high. Your kidneys are supposed to excrete 90% of your daily phosphate load. Your gastrointestinal tract excretes the remaining phosphate. When you have kidney problems, your phosphate levels can’t be regulated.

What is the FGF23 gene?

The FGF23 gene is located on chromosome 12 and codes for a 251-amino acid, 32 kDa pro-protein. Although FGF23 is predominantly expressed in and secreted by osteocytes and osteoblasts, lower levels of FGF23 expression have been detected in rodents in many non-bone tissues, including teeth and brain [ 16, 17, 18 ].

What is the relationship between FGF-23 and ADHR mutations?

) A mutation in FGF-23 gene enhances the processing of FGF-23 protein and causes tumoral calcinosis. J. Bone Miner. Res. (Abstr 1160). ) Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. –2086.

Does FGF23 play a role in the pathophysiology of XLH?

However, the expression of PHEX in myocytes indicates the potential for a more direct role for FGF23 in muscular weakness in XLH [ 74 ], and FGF23 has been shown to induce senescence in mesenchymal stem cells derived from skeletal muscle [ 189 ].

Does FGF23 promote myocardial fibrosis in mice?

Hao H., Li X., Li Q., et al. FGF23 promotes myocardial fibrosis in mice through activation of β-catenin. Oncotarget. 2016;7(40):64649–64664. doi: 10.18632/oncotarget.11623.

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