scholarly journals Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo

2011 ◽  
Vol 80 (5) ◽  
pp. 475-482 ◽  
Author(s):  
Ignacio López ◽  
M. Encarnación Rodríguez-Ortiz ◽  
Yolanda Almadén ◽  
Fátima Guerrero ◽  
A. Montes de Oca ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Indirect Effects ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Direct And Indirect Effects ◽  
Circulating Levels

scholarly journals Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men

2008 ◽  
Vol 158 (1) ◽  
pp. 125-129 ◽  
Author(s):  
Richard Marsell ◽  
Elin Grundberg ◽  
Tijana Krajisnik ◽  
Hans Mallmin ◽  
Magnus Karlsson ◽  
...  
Keyword(s):  
Renal Function ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Association Studies ◽  
Fibroblast Growth Factor 23 ◽  
Population Based ◽  
Fibroblast Growth

ObjectiveFibroblast growth factor-23 (FGF23) is a circulating factor involved in phosphate (Pi) and vitamin D metabolism. Serum FGF23 is increased at later stages of chronic kidney disease due to chronic hyperphosphatemia and decreased renal clearance. Recent studies also indicate that FGF23 may directly regulate the expression of parathyroid hormone (PTH) in vitro. Therefore, the objective of the current study was to determine the relationship between FGF23, PTH, and other biochemistries in vivo in subjects with no history of renal disease.DesignSerum biochemistries were measured in a subsample of the population-based Swedish part of the MrOS study. In total, 1000 Caucasian men aged 70–80 years were randomly selected from the population.MethodsIntact FGF23, Pi, calcium, albumin, estimated glomerular filtration rate (eGFR, calculated from cystatin C), PTH, and 25(OH)D3 were measured. Association studies were performed using linear univariate and multivariate regression analyses.ResultsThe median FGF23 level was 36.6 pg/ml, ranging from 0.63 to 957 pg/ml. There was a significant correlation between log FGF23 and eGFR (r=−0.21; P<0.00001) and log PTH (r=0.13; P<0.001). These variables remained as independent predictors of FGF23 in multivariate analysis. In addition, log PTH (β=0.082; P<0.05) and eGFR (β=−0.090; P<0.05) were associated with log FGF23 in subjects with eGFR>60 ml/min. Only eGFR (β=−0.35; P<0.0001) remained as a predictor of log FGF23 in subjects with eGFR<60 ml/min.ConclusionsSerum FGF23 and PTH are associated in vivo, supporting recent findings that FGF23 directly regulates PTH expression in vitro. Additionally, eGFR is associated with FGF23 in subjects with normal or mildly impaired renal function, indicating that GFR may modulate FGF23 levels independent of serum Pi.

Fibroblast Growth Factor 23 (FGF23) leads to endolysosomal routing of the renal phosphate co-transporters NaPi-IIa and NaPi-IIc in vivo

2021 ◽  
Author(s):  
Catharina J Küng ◽  
Betül Haykir ◽  
Udo Schnitzbauer ◽  
Daniela Egli-Spichtig ◽  
Nati Hernando ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Time Course ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Extracellular Signal ◽  
Early Endosomes ◽  
Lysosomal Proteases ◽  
Intracellular Pathway

The sodium-dependent phosphate co-transporters NaPi-IIa and NaPi-IIc located at the brush border membrane of renal proximal tubules are regulated by numerous factors, including fibroblast growth factor 23 (FGF23). FGF23 downregulates NaPi-IIa and NaPi-IIc abundance after activating a signaling pathway involving phosphorylation of the extracellular signal-regulated protein kinase (phospho-ERK1/2). FGF23 also downregulates the expression of renal 1-α-hydroxylase (Cyp27b1) and upregulates 24-hydroxylase (Cyp24a1), thus reducing plasma calcitriol levels. Here, we examined the time course of the FGF23-induced internalization of NaPi-IIa and NaPi-IIc and their intracellular pathway towards degradation in vivo. Mice were injected intraperitoneally with recombinant human FGF23 (rh-FGF23) in the absence (biochemical analysis) or presence (immunohistochemistry) of leupeptin, an inhibitor of lysosomal proteases. Phosphorylation of ERK1/2 was enhanced 60 minutes after rh-FGF23 administration, and increased phosphorylation was still detected 480 minutes post-injection. Co-localization of phospho-ERK1/2 with NaPi-IIa was seen at 60, 120 and partly at 480 minutes. The abundance of both co-transporters was reduced 240 minutes after rh-FGF23 administration, with a further reduction at 480 minutes. NaPi-IIa and NaPi-IIc were found to co-localize with clathrin and early endosomal antigen 1 (EEA1) as early as 120 minutes after rh-FGF23 injection. Both co-transporters partially co-localized with cathepsin B and Lamp1, markers of lysosomes, 120 minutes after rh-FGF23 injection. Thus, NaPi-IIa and NaPi-IIc are internalized within 2 hours upon rh-FGF23 injection. Both co-transporters share the pathway of clathrin-mediated endocytosis that leads first to early endosomes, finally resulting in trafficking towards the lysosome as early as 120 minutes after rh-FGF23 administration.

scholarly journals Convergent Signaling Pathways Regulate Parathyroid Hormone and Fibroblast Growth Factor-23 Action on NPT2A-mediated Phosphate Transport

2016 ◽  
Vol 291 (36) ◽  
pp. 18632-18642 ◽  
Author(s):  
W. Bruce Sneddon ◽  
Giovanni W. Ruiz ◽  
Luciana I. Gallo ◽  
Kunhong Xiao ◽  
Qiangmin Zhang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Phosphate Transport ◽  
Fibroblast Growth

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 Spleen contributes significantly to increased circulating levels of fibroblast growth factor 23 in response to lipopolysaccharide-induced inflammation

2016 ◽  
Vol 32 (6) ◽  
pp. 960-968 ◽  
Author(s):  
Shweta Bansal ◽  
William E. Friedrichs ◽  
Chakradhar Velagapudi ◽  
Denis Feliers ◽  
Khaled Khazim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Circulating Levels
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