PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop.

@article{LaviMoshayoff2010PTHIF,
  title={PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop.},
  author={Vardit Lavi-Moshayoff and Gilad Wasserman and Tomer Meir and Justin Silver and Tally Naveh-Many},
  journal={American journal of physiology. Renal physiology},
  year={2010},
  volume={299 4},
  pages={
          F882-9
        }
}
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) target the kidney to cause a phosphaturia. FGF23 also acts on the parathyroid to decrease PTH expression, but in chronic kidney disease (CKD) there are high-serum PTH and FGF23 levels and resistance of the parathyroid to FGF23. We now report that PTH acts on bone to increase FGF23 expression and characterize the signal transduction pathway whereby PTH increases FGF23 expression. Remarkably, we show that PTH is necessary for the… 
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Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia
TLDR
FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor and when increased PTH gland secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished.
FGF23 and the parathyroid.
TLDR
There is down-regulation of parathyroid klotho-FGFR1 in CKD which correlates with the resistance of the parathyroids to FGF23, suggesting a negative feedback loop between bone and theParathyroid.
Fgf23 and parathyroid hormone signaling interact in kidney and bone
Calcium deficiency reduces circulating levels of FGF23.
TLDR
In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus, which suggests that hypocalcemia reduces the circulating concentrations of FGF 23.
Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis.
TLDR
The pathogenesis of secondary hyperparathyroidism is discussed, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD, with implications for the deeper understanding of disordered mineral metabolism in CKD.
The fibroblast growth factor receptor mediates the increased FGF23 expression in acute and chronic uremia.
TLDR
A derangement in FGF23 regulation starts early in the course of acute kidney injury, is in part independent of the increase in serum PTH, and involves activation of FGFR1.
Phosphorus and Kidney Disease: Mechanisms for Perturbed Phosphorus Homeostasis in Chronic Kidney Disease
TLDR
The major focus of this chapter will be to understand the mechanism of abnormal phosphorus homeostasis in patients with kidney disease, with particular attention to the biochemical/hormonal factors including vitamin D, PTH, and FGF23, as well as a brief consideration of bone and the intestine.
FGF-23 and secondary hyperparathyroidism in chronic kidney disease
TLDR
The mechanisms by which secondary hyperparathyroidism associated with CKD stimulates bone cells to overexpress FGF-23 levels are discussed, which includes local changes in the ratio of inorganic phosphate to pyrophosphate in bone.
Calcium De fi ciency Reduces Circulating Levels of FGF 23
TLDR
The hypothesis is that because increased calcitriol values are necessary to correct hypocalcemia in conditions of calcium deficiency, a calcriol-induced increase in FGF23 might be prevented when serum calcium levels are low.
Relationship between GFR, intact PTH, oxidized PTH, non‐oxidized PTH as well as FGF23 in patients with CKD
  • Shufei Zeng, U. Querfeld, +14 authors B. Hocher
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2020
Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism. In chronic kidney disease (CKD), circulating FGF23 and PTH…
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References

SHOWING 1-10 OF 56 REFERENCES
The parathyroid is a target organ for FGF23 in rats.
TLDR
It is shown that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH, which adds a new dimension to the understanding of mineral homeostasis.
Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells.
TLDR
FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro, which defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism.
Regulation of Fibroblast Growth Factor 23 Production in Bone in Uremic Rats
TLDR
Elevated plasma F GF23 levels in uremic rats reflect the increased expression of FGF23 in bone, which may be regulated by a PTH-1,25(OH)2D3 axis-dependent pathway and another PTH/PTH-dependent and 1,25-dihydroxyvitamin D/D3-independent pathway in u Remic rats.
Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease.
TLDR
Because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease, and in vivo resistance is sustained inParathyroid organ culture in vitro.
Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats.
Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated…
Parathyroid hormone signaling in bone and kidney
TLDR
Recent studies demonstrate the involvement of novel factors as well as additional roles for previously identified downstream factors of PTH, both as a mediator and regulator.
FGF-23 in patients with end-stage renal disease on hemodialysis.
TLDR
Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis and may provide new insights into the pathophysiologic effects of F GF-23 on calcium-phosphate homeostasis.
Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.
TLDR
In vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3, and posttranscriptional, affecting PTH at a translational or posttranslational step.
Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism.
TLDR
It is found that PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone.
Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients.
TLDR
The results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients.
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