Regulation of fibroblast growth factor 23 (<scp>FGF</scp>23) in health and disease

Bär, Ludmilla; Stournaras, Christos; Läng, Florian; Föller, Michael

doi:10.1002/1873-3468.13494

Cited by 59 publications

(45 citation statements)

References 289 publications

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“…Accordingly, FGF-23 constitutes the link between erythropoiesis and bone homeostasis in both physiological, as well as in a variety of pathological conditions [156,157]. Indeed, we recently showed increased FGF-23 levels associated with ineffective erythropoiesis and impaired bone mineralization in myelodysplastic syndromes (MDS) [158].…”

Section: Hif-epo-fgf23 Axis: Phd2/hif Inhibitionmentioning

confidence: 99%

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

Watts

Gaete

Rodríguez

et al. 2020

Preprint

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Erythropoiesis is a complex process driving the production of red blood cells. During homeostasis, adult erythropoiesis takes place in the bone marrow and is tightly controlled by erythropoietin (EPO), a central hormone mainly produced in renal EPO-producing cells. The expression of EPO is strictly regulated by local changes in oxygen partial pressure (pO2) as under deprived oxygen (hypoxia) the transcription factor Hypoxia Inducible Factor-2 induces EPO. However, erythropoiesis regulation extends beyond the well-established HIF-EPO axis, and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism. The importance of a number of these factors is evident as their altered expression has been associated with various anemia-related disorders, including chronic kidney disease. Eventually, our emerging understanding of HPPs and their regulatory feedback will be instrumental in developing specific therapies for anemic patients and beyond.

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Section: Hif-epo-fgf23 Axis: Phd2/hif Inhibitionmentioning

confidence: 99%

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

Watts

Gaete

Rodríguez

et al. 2020

Preprint

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“…135 Klotho as an Obligatory Co-receptor High concentrations of phosphate in the body are found in bone, teeth, and dental enamel as calcium phosphate crystals. 136,137 Klotho regulates phosphorus and calcium homeostasis 5,6,18,23,138 and functions as an obligatory co-receptor that binds and activates its related endocrine fibroblast growth factor (FGF) receptors (FGFRs) to potentiate its biological activities. 5,6,23,102,[139][140][141][142][143][144][145][146] FGFs are exemplary pleiotropic hormones that play numerous roles in cellular and metabolic homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…5,6,23,102,[139][140][141][142][143][144][145][146] FGFs are exemplary pleiotropic hormones that play numerous roles in cellular and metabolic homeostasis. 5,6,137,141,[144][145][146][147][148] In particular, FGF23 is a bone-derived hormone that in conjunction with Klotho acts on the kidney to increase phosphate excretion and suppress biosynthesis of vitamin D. 5,6,14,23,102,136,138,145,148,149 Vitamin D regulates epigenetic mechanisms that maintain the transcription of its target genes in regulatory networks, including the expression of Klotho and nuclear factor-erythroid-2related factor 2 (Nrf2) to carry out many of its homoeostatic functions. 17,97,[150][151][152][153] Vitamin D is a modulator of the immune system, 154,155 hence its mention here, and accumulating evidence suggests vitamin D deficiency is a risk factor for dysregulated Klotho-associated neurodegenerative diseases, the most noteworthy being MS. 9,27,52,97,…”

Section: Introductionmentioning

confidence: 99%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

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In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

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“…Paracrine actions of FGF23 include the regulation of immune cell, hepatocyte, and cardiomyocyte function, to name a few. The renal effects of FGF23 are mediated by a specific membrane fibroblast growth factor receptor (FGFR) which forms a complex with transmembrane protein αKlotho that can be cleaved resulting in soluble Klotho . The induction of cardiac hypertrophy, however, is accomplished by FGF23 without the contribution of αKlotho …”

Section: Introductionmentioning

confidence: 99%

Endothelin receptor B controls the production of fibroblast growth factor 23

et al. 2020

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Endothelin-1 (ET-1) is a member of the endothelin family of peptide hormones first discovered as endothelium-derived mediators regulating vascular tone. ET-1 also regulates the proliferation and differentiation of bone cells that synthesize fibroblast growth factor 23 (FGF23). FGF23 is a hormone controlling renal phosphate and vitamin D metabolism. Here, we studied the role of ET-1 and endothelin receptor B (ETB) for FGF23 production. Fgf23 gene expression was studied in IDG-SW3 bone cells by quantitative RT-PCR. ETB-expressing (etb +/+ ) and rescued ETBdeficient mice (etb −/− ) were studied in metabolic cages. Their serum FGF23, PTH, and 1,25(OH) 2 D 3 concentrations were determined by ELISA, serum and urinary phosphate and Ca 2+ by photometric methods. ET-1 and ETB agonist sarafotoxin 6c suppressed Fgf23 mRNA in IDG-SW3 cells. Serum C-terminal and intact FGF23 as well as bone Fgf23 mRNA levels were significantly higher in etb −/− mice than in etb +/+ mice. Renal phosphate excretion was significantly higher in etb −/− mice despite lower phosphate levels. In addition, etb −/− animals exhibited calciuria and a significantly higher serum 1,25(OH) 2 D 3 concentration compared to etb +/+ mice. In conclusion, ETB-dependent ET-1 signaling is a potent suppressor of FGF23 formation. This effect is likely to be of clinical relevance given the use of endothelin receptor antagonists in various diseases. K E Y W O R D SET-1, klotho, phosphate, vitamin D

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Regulation of fibroblast growth factor 23 (FGF23) in health and disease

Cited by 59 publications

References 289 publications

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Endothelin receptor B controls the production of fibroblast growth factor 23

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