FGF23/Klotho New Regulators of Vitamin D Metabolism

David, Véronique; Quarles, L. Darryl

doi:10.1016/b978-0-12-381978-9.10042-3

Cited by 3 publications

(3 citation statements)

References 158 publications

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“…Whole femurs were analyzed as previously described. 12 , 59 Cells were cultured in 75 cm 2 flasks for 12 days before treatment. 4 mL culture medium was filtered through a 50KDa ultra centrifugation column (EMD Millipore) and dried overnight in a Savant SpeedVac system (Thermo Fisher Scientific, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“… 1 FGF23 inhibits renal phosphate reabsorption by downregulating expression of the sodium-phosphate cotransporters NPT2a and NPT2c, and decreases circulating 1,25-dihydroxyvitamin D 3 levels by inhibiting renal expression of CYP27B1 (1-α-hydroxylase) and stimulating expression of CYP24A1 (24-hydroxylase). 2 , 3 FGF23 levels rise progressively in chronic kidney disease (CKD), and higher levels are strongly associated with increased risks of CKD progression, cardiovascular events, and mortality. 4 - 9 Experimental data suggesting that FGF23 may contribute causally to certain cardiovascular complications of CKD 10 emphasize the therapeutic importance of defining the molecular mechanisms that stimulate FGF23 production beginning early in the course of CKD.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production

David

Martin

Isakova

et al. 2016

Kidney International

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Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with chronic kidney disease (CKD), but the mechanisms are poorly understood. Here we tested whether inflammation and iron deficiency regulate FGF23. In wild-type mice, acute inflammation induced by single injections of heat-killed Brucella abortus or interleukin-1β (IL-1β) decreased serum iron within 6 hours, and was accompanied by significant increases in osseous Fgf23 mRNA expression and serum levels of C-terminal FGF23, but no changes in intact FGF23. Chronic inflammation induced by repeated bacteria or IL-1β injections decreased serum iron, increased osseous Fgf23 mRNA and serum C-terminal FGF23, but modestly increased biologically active, intact FGF23 serum levels. Chronic iron deficiency mimicked chronic inflammation. Increased osseous FGF23 cleavage rather than a prolonged half-life of C-terminal FGF23 fragments accounted for the elevated C-terminal FGF23 but near-normal intact FGF23 levels in inflammation. IL-1β injection increased Fgf23 mRNA and C-terminal FGF23 levels similarly in wild-type and Col4a3KO mice with CKD, but markedly increased intact FGF23 levels only in the CKD mice. Inflammation increased Fgf23 transcription by activating Hif1α signaling. Thus, inflammation and iron deficiency stimulate FGF23 production. Simultaneous upregulation of FGF23 cleavage in osteocytes maintains near-normal levels of biologically active, intact circulating FGF23, whereas downregulated or impaired FGF23 cleavage may contribute to elevated intact serum FGF23 in CKD.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production

David

Martin

Isakova

et al. 2016

Kidney International

Self Cite

404

456

View full text Add to dashboard Cite

show abstract

“…FGF23 primarily targets the kidney to decrease the sodium phosphate cotransporters NPT2a and NPT2c and to reduce 1,25-dihydroxyvitamin D [1,25(OH) 2 D] production by inhibiting the renal 1␣ hydroxylase (Cyp27b1) and stimulating the catabolic 24-hydroxylase (Cyp24a1) ( Fig. 1) (17,28). The net effect is to limit intestinal phosphate absorption and to inhibit renal phosphate reabsorption.…”

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confidence: 99%

Ironing out the cross talk between FGF23 and inflammation

David

Francis

Babitt

2017

American Journal of Physiology-Renal Physiology

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The bone-secreted hormone fibroblast growth factor 23 (FGF23) has an essential role in phosphate homeostasis by regulating expression of the kidney proximal tubule sodium-phosphate cotransporters as well as parathyroid hormone levels. Induction of FGF23 early in chronic kidney disease (CKD) helps to maintain normal phosphorous levels. However, high FGF23 levels become pathological as kidney disease progresses and are associated with an increased risk of CKD progression, cardiovascular events, and death. The factors responsible for increasing FGF23 levels early in CKD are unknown, but recent work has proposed a role for inflammation and disordered iron homeostasis. Notably, FGF23 has recently been shown to elicit an inflammatory response and to display immunomodulatory properties. Here, we will review emerging evidence on the cross talk between inflammation, iron, FGF23, and bone and mineral metabolism and discuss the relevance for CKD patients.

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Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis

et al. 2022

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Blood levels of the vitamin D3 (D3) metabolites 25-hydroxyvitamin D3 (25(OH)D3), 24R,25-dihydroxyvitamin D3, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) are recognized indicators for the diagnosis of bone metabolism-related diseases, D3 deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D3 metabolites, such as 20-hydroxyvitamin D3 and lactone D3, also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum. Here, we describe a versatile synthesis of deuterium-labeled D3 metabolites using A-ring synthons containing three deuterium atoms. Deuterium-labeled 25(OH)D3 (2), 25(OH)D3-23,26-lactone (6), and 1,25(OH)2D3-23,26-lactone (7) were synthesized, and successfully applied as internal standards for the measurement of these compounds in pooled human serum. This is the first quantification of 1,25(OH)2D3-23,26-lactone (7) in human serum.

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FGF23/Klotho New Regulators of Vitamin D Metabolism

Cited by 3 publications

References 158 publications

Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production

Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production

Ironing out the cross talk between FGF23 and inflammation

Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis

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