scholarly journals FGF23 as a calciotropic hormone

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1472 ◽  
Author(s):  
María E. Rodríguez-Ortiz ◽  
Mariano Rodríguez
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Calcium Homeostasis ◽  
Bone Cells ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Calcium Deficiency ◽  
Fibroblast Growth

Maintaining mineral metabolism requires several organs and hormones. Fibroblast growth factor 23 (FGF23) is a phosphatonin produced by bone cells that reduces renal production of calcitriol – 1,25(OH)2D3 – and induces phosphaturia. The consequences of a reduction in 1,25(OH)2D3 involve changes in calcium homeostasis. There are several factors that regulate FGF23: phosphorus, vitamin D, and parathyroid hormone (PTH). More recently, several studies have demonstrated that calcium also modulates FGF23 production. In a situation of calcium deficiency, the presence of 1,25(OH)2D3 is necessary to optimize intestinal absorption of calcium, and FGF23 is decreased to avoid a reduction in 1,25(OH)2D3 levels.

scholarly journals Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5269-5279 ◽  
Author(s):  
Xiuying Bai ◽  
Dengshun Miao ◽  
Jiarong Li ◽  
David Goltzman ◽  
Andrew C. Karaplis
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Fibroblast Growth Factor ◽  
Calcium Homeostasis ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Circulating Levels

Abstract Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.

scholarly journals 25-vitamin D, 1,25-vitamin D, parathyroid hormone, fibroblast growth factor-23 and cognitive function in men with advanced CKD: a veteran population

2014 ◽  
Vol 82 (2014) (11) ◽  
pp. 296-303 ◽  
Author(s):  
Anna J. Jovanovich ◽  
Michel Chonchol ◽  
Christopher B. Brady ◽  
James D. Kaufman ◽  
Jessica Kendrick ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Cognitive Function ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

scholarly journals Parathyroid hormone or fibroblast growth factor 23? Which one is the main determinant of the hypophosphatemia after kidney transplantation?

2018 ◽  
Vol 8 (2) ◽  
pp. 86-90 ◽  
Author(s):  
Seyed Sadroddin Rasi Hashemi ◽  
Zahra Navarbaf ◽  
Amir Ghorbanihaghjo ◽  
Morteza Ghojazadeh ◽  
Jalal Etemadi ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Parathyroid Hormone ◽  
Renal Transplantation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Kidney Transplant Recipients ◽  
Endstage Renal Disease

Introduction: Kidney transplantation restores many of the disorders accompanying endstage renal disease (ESRD). However, hypophosphatemia is common complication after renal transplantation. High levels of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are two suspected factors determining the hypophosphatemia after kidney transplantation. Objectives: This observational prospective study was carried out to clarify the role of mentioned factors in hypophosphatemia after kidney transplantation. Patients and Methods: Living donor kidney transplant recipients which admitted to the ward of the renal transplantation, enrolled to the study. Parameters of bone and mineral metabolism including FGF23 and intact PTH levels were assessed. Results: High FGF23 level before transplantation was related to lower phosphate levels at 3rd month after transplantation. PTH levels showed no relationship with hypophosphatemia after kidney transplantation. Conclusion: High levels of FGF23 in ESRD patients undergoing kidney transplantation is an important determinant of hypophosphatemia in long-term follow up.

scholarly journals Fibroblast growth factor-23 regulates parathyroid hormone and 1α-hydroxylase expression in cultured bovine parathyroid cells

2007 ◽  
Vol 195 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Tijana Krajisnik ◽  
Peyman Björklund ◽  
Richard Marsell ◽  
Östen Ljunggren ◽  
Göran Åkerström ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Level ◽  
Serum Levels ◽  
Negative Regulator ◽  
Fibroblast Growth

Fibroblast growth factor-23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate (Pi) as well as 1,25-dihydroxyvitamin D3. Recent studies also suggest a correlation between serum levels of FGF23 and parathyroid hormone (PTH) in patients with chronic kidney disease. It is, however, unknown whether FGF23 directly modulates PTH expression, or whether the correlation is secondary to abnormalities in Pi and vitamin D metabolism. The objective of the current study was therefore to elucidate possible direct effects of FGF23 on bovine parathyroid cells in vitro. Treatment of parathyroid cells with a stabilized form of recombinant FGF23 (FGF23(R176Q)) induced a rise in early response gene-1 mRNA transcripts, a marker of FGF23 signaling. FGF23(R176Q) potently and dose-dependently decreased the PTH mRNA level within 12 h. In agreement, FGF23(R176Q) also decreased PTH secretion into conditioned media. In contrast, FGF23(R176Q) dose-dependently increased 1α-hydroxylase expression within 3 h. FGF23 (R176Q) did not affect cell viability nor induce apoptosis, whereas a small but significant increase in cell proliferation was found. We conclude that FGF23 is a negative regulator of PTH mRNA expression and secretion in vitro. Our data suggest that FGF23 may be a physiologically relevant regulator of PTH. This defines a novel function of FGF23 in addition to the previously established roles in controlling vitamin D and Pi metabolism.

scholarly journals Fibroblast Growth Factor 23 Associates with Death in Critically Ill Patients

2018 ◽  
Vol 13 (4) ◽  
pp. 531-541 ◽  
Author(s):  
David E. Leaf ◽  
Edward D. Siew ◽  
Michele F. Eisenga ◽  
Karandeep Singh ◽  
Finnian R. Mc Causland ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Confidence Interval ◽  
Fibroblast Growth Factor ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Vitamin D Metabolites ◽  
Fibroblast Growth

Background and objectives Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D–regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI.Design, setting, participants, & measurementsWe measured plasma FGF23 and other mineral metabolite levels in two cohorts of critically ill patients (n=1527). We included 817 patients with AKI requiring RRT who enrolled in the ARF Trial Network (ATN) study, and 710 patients with and without AKI who enrolled in the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study. We hypothesized that higher FGF23 levels at enrollment are independently associated with higher 60-day mortality.ResultsIn the ATN study, patients in the highest compared with lowest quartiles of C-terminal (cFGF23) and intact FGF23 (iFGF23) had 3.84 (95% confidence interval, 2.31 to 6.41) and 2.08 (95% confidence interval, 1.03 to 4.21) fold higher odds of death, respectively, after adjustment for demographics, comorbidities, and severity of illness. In contrast, plasma/serum levels of parathyroid hormone, vitamin D metabolites, calcium, and phosphate were not associated with 60-day mortality. In the VALID study, patients in the highest compared with lowest quartiles of cFGF23 and iFGF23 had 3.52 (95% confidence interval, 1.96 to 6.33) and 1.93 (95% confidence interval, 1.12 to 3.33) fold higher adjusted odds of death.ConclusionsHigher FGF23 levels are independently associated with greater mortality in critically ill patients.

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