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| http://purl.uniprot.org/citations/33049075 | http://www.w3.org/2000/01/rdf-schema#comment | "Fibroblast growth factor 23 (FGF23) is a key phosphate- and vitamin D-regulating hormone. FGF23 circulates as an intact 251 amino acid protein or N- and C-terminal degradation products. Hormone activity resides in the intact molecule, but it has been suggested that high levels of the C-terminal protein can interfere with intact FGF23 (iFGF23) activity. New evidence points to involvement of the hypoxia-inducible factor (HIF)/erythropoietin (EPO)/iron pathway as important in FGF23 physiology. Exactly how this pathway regulates FGF23 is not clear. Various in vitro, in vivo, and clinical studies involving perturbations in this pathway at various points have yielded conflicting results. Many of these studies are complicated by the confounding, independent effect of renal insufficiency on FGF23. To gain insight into FGF23 physiology, we studied 8 patients with a rare paraganglioma/somatostatinoma syndrome who had elevated blood EPO levels as a result of somatic gain-of-function mutations in HIF2A (EPAS1) that stimulate tumoral EPO production. All patients had normal renal function. EPO levels varied; most were very elevated and highly correlated with C-terminal FGF23 (cFGF23) levels that were also markedly elevated. Blood phosphate and intact FGF23 levels were normal. These data from patients with normal renal function in whom HIF activation was the inciting event suggest a direct role of the HIF/EPO pathway in FGF23 transcription and translation. They also demonstrate that posttranslational regulation was finely tuned to maintain normal blood phosphate levels. Additionally, normal phosphate and intact FGF23 levels in the setting of markedly increased C-terminal FGF23 levels suggest intact FGF23 action is not attenuated by C-terminal FGF23. Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.org/dc/terms/identifier | "doi:10.1002/jbmr.4195"xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Brown S."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Pang Y."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Zhuang Z."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Huynh T."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Pacak K."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Collins M.T."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/author | "Roszko K.L."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/name | "J Bone Miner Res"xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/pages | "315-321"xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/title | "C-Terminal, but Not Intact, FGF23 and EPO Are Strongly Correlatively Elevated in Patients With Gain-of-Function Mutations in HIF2A: Clinical Evidence for EPO Regulating FGF23."xsd:string |
| http://purl.uniprot.org/citations/33049075 | http://purl.uniprot.org/core/volume | "36"xsd:string |
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