Affinage

FGF23

Fibroblast growth factor 23 · UniProt Q9GZV9

Round 2 corrected
Length
251 aa
Mass
28.0 kDa
Annotated
2026-04-28
130 papers in source corpus 42 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF23 is a bone-derived endocrine hormone that governs systemic phosphate and vitamin D homeostasis and exerts pleiotropic actions on the heart, immune cells, erythropoiesis, and iron metabolism. Intact FGF23 signals through a ternary complex of FGFR1c and the co-receptor α-Klotho — whose crystal structure reveals Klotho as a non-enzymatic scaffold tethering FGF23's C-terminal tail to FGFR1c's D3 domain — activating FRS2/RAS/RAF/MEK/ERK1/2 in the kidney to suppress NaPi-2a/NaPi-2c phosphate cotransporters and 1α-hydroxylase, and in the parathyroid to suppress PTH secretion (PMID:29342138, PMID:17086194, PMID:19515808, PMID:17992255). The biological activity of FGF23 is determined by competing post-translational modifications: O-glycosylation by GALNT3 at the RXXR motif protects intact FGF23 from FURIN/proprotein convertase cleavage, whereas FAM20C-mediated phosphorylation promotes cleavage to inactive N- and C-terminal fragments — mutations disrupting the RXXR site cause autosomal dominant hypophosphatemic rickets (ADHR), and loss of GALNT3 causes familial tumoral calcinosis (PMID:11062477, PMID:16638743, PMID:26746780). Beyond phosphate regulation, FGF23 induces Klotho-independent cardiac hypertrophy via FGFR4/PLCγ/calcineurin/NFAT signaling, inhibits neutrophil integrin activation through FGFR2/PKA/Rap1, suppresses erythropoiesis, and its C-terminal cleavage fragments counteract BMP2/9-induced hepcidin to regulate iron homeostasis during inflammation (PMID:21985788, PMID:26878171, PMID:24509850, PMID:37053547).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Positional cloning identified FGF23 as a novel secreted FGF family member and established that missense mutations at the RXXR cleavage motif cause autosomal dominant hypophosphatemic rickets, linking FGF23 for the first time to phosphate homeostasis.

    Evidence Positional cloning, genomic sequencing, and cDNA expression in insect cells

    PMID:11032749 PMID:11062477

    Open questions at the time
    • Mechanism of FGF23-mediated phosphate wasting unknown
    • Target receptor unidentified
    • Regulation of FGF23 expression unknown
  2. 2001 High

    Demonstration that only intact full-length FGF23 is phosphaturic — and that ADHR mutations render FGF23 resistant to RXXR-site proteolysis — established proteolytic cleavage as the primary inactivation mechanism and explained the gain-of-function nature of ADHR.

    Evidence Recombinant FGF23 injection in mice, CHO implantation model, site-directed mutagenesis in HEK293 cells with fragment-specific antibodies

    PMID:11344269 PMID:11737582

    Open questions at the time
    • Identity of the protease(s) cleaving FGF23 at RXXR not determined
    • Whether post-translational modifications regulate cleavage unknown
  3. 2002 High

    In vivo studies using cleavage-resistant FGF23 and thyroparathyroidectomized animals proved that FGF23 suppresses renal phosphate reabsorption and 1,25(OH)₂D independently of PTH, defining FGF23 as an autonomous phosphaturic hormone.

    Evidence Naked DNA injection, protein infusion in thyroparathyroidectomized rats, Na/Pi co-transport assays

    PMID:12130585 PMID:12419819

    Open questions at the time
    • Receptor mediating renal FGF23 effects unidentified
    • Direct target genes in kidney unknown
  4. 2003 High

    Detailed time-course experiments revealed that FGF23 reduces NaPi-2a protein and suppresses 1α-hydroxylase while inducing 24-hydroxylase before any change in serum phosphate, establishing these as direct renal actions; PHEX was excluded as a direct FGF23 protease.

    Evidence FGF23 injection in normal and parathyroidectomized rats with sequential renal mRNA/protein analysis; in vitro PHEX cleavage assays

    PMID:12874285 PMID:15040831

    Open questions at the time
    • Exact renal signaling pathway downstream of FGF23 undefined
    • How PHEX mutations elevate FGF23 transcription mechanistically unclear
  5. 2006 High

    The identification of Klotho as an obligate co-receptor that converts FGFR1c into a high-affinity FGF23 receptor solved the receptor specificity problem for this endocrine FGF, explaining tissue-specific signaling restricted to Klotho-expressing organs.

    Evidence Renal homogenate pull-down, forced Klotho expression restoring FGF23 responsiveness, receptor binding assays, anti-Klotho antibody in vivo

    PMID:17086194

    Open questions at the time
    • Atomic details of the ternary complex unknown
    • Whether other FGFRs participate in specific tissues unclear
  6. 2006 High

    GALNT3-mediated O-glycosylation at the RXXR motif was shown to block proprotein convertase cleavage, establishing a glycosylation–proteolysis competition that governs the ratio of intact to cleaved FGF23 and explaining tumoral calcinosis from GALNT3 loss.

    Evidence Cell-based glycosylation/processing assays with mutagenesis and mass spectrometry

    PMID:16638743

    Open questions at the time
    • Identity of the specific convertase(s) acting in vivo on FGF23 not fully resolved
    • How FAM20C phosphorylation opposes glycosylation not yet demonstrated
  7. 2007 High

    FGF23 was found to act directly on the parathyroid gland via Klotho/FGFR-dependent MAPK/ERK signaling to suppress PTH secretion and gene expression, extending FGF23's endocrine axis beyond the kidney.

    Evidence FGF23 administration in rats, in vitro parathyroid cultures, MAPK inhibitor blockade, ERK phosphorylation assays

    PMID:17992255

    Open questions at the time
    • Whether FGF23 regulation of PTH is physiologically dominant over calcium sensing unknown
    • Contribution of specific FGFRs in parathyroid not defined
  8. 2009 High

    Conditional knockout of FGFR1 in kidney abolished FGF23-induced phosphaturia, while the C-terminal tail of FGF23 was shown to mediate binding at the FGFR1c–Klotho interface and act as a competitive inhibitor in vivo, defining FGFR1 as the principal renal FGF23 receptor and the C-tail as the Klotho-binding domain.

    Evidence Conditional FGFR1-KO mice, FGFR3/4-KO mice, ternary complex reconstitution in vitro, C-terminal peptide injection in rats and Hyp mice

    PMID:19515808 PMID:19966287

    Open questions at the time
    • High-resolution structure of the ternary complex still lacking
    • Role of heparan sulfate in complex assembly not resolved
  9. 2011 High

    FGF23 was discovered to cause left ventricular hypertrophy through Klotho-independent, FGFR-dependent calcineurin/NFAT activation in cardiomyocytes, revealing an off-target cardiac toxicity pathway relevant to CKD.

    Evidence Cardiomyocyte hypertrophy assays, intramyocardial FGF23 injection, Klotho-KO mice with LVH, CKD model with FGFR blocker

    PMID:21985788

    Open questions at the time
    • Which FGFR mediates cardiac effects not initially identified
    • Whether cardiac Klotho absence is truly absolute debated
  10. 2015 Medium

    Multiple inputs regulating FGF23 transcription in osteocytes were mapped: phosphate acts via ROS/MEK-ERK, 1,25D via a composite ETS1-VDR/Nurr1 promoter element, inflammatory cytokines via NF-κB, and FAM20C phosphorylation was shown to oppose GALNT3-mediated protection from convertase cleavage, completing the post-translational processing picture.

    Evidence Promoter-luciferase reporters with mutagenesis, pharmacological inhibitors in osteoblast cell lines, in vitro cleavage assays with recombinant convertases, IDG-SW3 osteocyte cultures

    PMID:25458698 PMID:25792238 PMID:26148725 PMID:26746780

    Open questions at the time
    • In vivo validation of individual promoter elements lacking
    • Relative contribution of each convertase in osteocytes unclear
    • Integration of multiple transcriptional inputs not modeled quantitatively
  11. 2015 High

    EGR-1 was identified as a key transcription factor downstream of FGF23/ERK signaling in kidney that mediates the phosphaturic but not the vitamin D–suppressive arm of FGF23 action, revealing bifurcation of FGF23 renal signaling.

    Evidence FGF23 injection in Egr1-KO and Hyp/Egr1-KO mice, ChIP-seq for EGR-1 cistrome in kidney

    PMID:26588476

    Open questions at the time
    • Transcription factors mediating the 1,25D arm of FGF23 action not identified
    • Direct EGR-1 target genes responsible for NaPi-2a/2c downregulation not confirmed
  12. 2016 High

    FGF23 was shown to impair neutrophil recruitment via FGFR2/PKA-mediated inhibition of Rap1 and β2-integrin activation, establishing a mechanism for FGF23-driven immunosuppression in CKD independently of Klotho.

    Evidence Intravital microscopy in CKD mice, FGF23 neutralization, PMN adhesion assays, FGFR2 and PKA knockdown

    PMID:26878171

    Open questions at the time
    • Effects on other leukocyte populations not assessed
    • Whether this mechanism operates in non-CKD contexts unknown
  13. 2018 High

    The crystal structure of the α-Klotho–FGFR1c–FGF23 ternary complex revealed that Klotho acts as a non-enzymatic scaffold simultaneously engaging FGFR1c's D3 domain and FGF23's C-terminal tail, and that heparan sulfate is additionally required for receptor dimerization and activation.

    Evidence X-ray crystallography at atomic resolution with structure-function validation

    PMID:29342138

    Open questions at the time
    • Structure of the activated dimeric signaling complex not resolved
    • Structural basis for FGFR4-mediated Klotho-independent signaling unknown
  14. 2018 High

    Cardiac hypertrophic signaling by FGF23 was attributed specifically to FGFR4 and PLCγ/calcineurin/NFAT, while insulin/IGF1 were shown to suppress FGF23 transcription via PI3K/Akt/FOXO1, connecting metabolic status to FGF23 output.

    Evidence FGFR4-specific inhibitors in cardiomyocytes; insulin/IGF1 treatment of osteoblasts with PI3K/Akt inhibitors, streptozotocin-diabetic mice, human OGTT correlation

    PMID:29760049 PMID:29892269

    Open questions at the time
    • Whether FGFR4 is necessary in vivo for FGF23-induced LVH not tested genetically at this point
    • Relative contribution of FOXO1 versus other insulin-regulated transcription factors in vivo unclear
  15. 2018 High

    FGF23 was found to increase NCC membrane expression in the distal nephron via ERK1/2/SGK1/WNK4, linking FGF23 to sodium retention, volume expansion, and hypertension in a Klotho-dependent manner.

    Evidence Mouse models of Fgf23/Klotho deficiency, Hyp mice, chlorothiazide rescue, NCC membrane fractionation

    PMID:24797667

    Open questions at the time
    • Contribution of FGF23-driven sodium retention to CKD hypertension relative to other mechanisms not quantified
    • Whether this pathway operates in normal physiology or only in pathological FGF23 excess unclear
  16. 2020 High

    Kidney-derived glycerol-3-phosphate was identified as a circulating signal that stimulates bone FGF23 production via GPAT-mediated LPA synthesis and LPAR1 receptor activation, revealing a kidney-to-bone metabolic signaling axis.

    Evidence LC-MS metabolomics and aptamer proteomics of renal venous plasma, G-3-P/LPA administration, GPAT inhibition, Lpar1-KO mice, AKI models

    PMID:32065590

    Open questions at the time
    • Downstream intracellular signaling from LPAR1 to FGF23 transcription not mapped
    • Whether G-3-P contributes to FGF23 elevation in CKD (not just AKI) untested
  17. 2021 High

    Ectopic hepatic FGF23 production was shown to be driven by an IL-6/ERR-γ transcriptional axis during AKI, identifying the liver as a non-canonical FGF23 source in acute disease.

    Evidence Liver-specific ERR-γ KO mice, hepatocyte-specific FGF23 KO, IL-6 neutralization, ERR-γ inverse agonist, folic acid AKI model

    PMID:33853949

    Open questions at the time
    • Whether hepatic FGF23 is biologically processed differently from osteocyte-derived FGF23 unknown
    • Functional consequences of liver-derived FGF23 on mineral metabolism not separated from bone-derived FGF23
  18. 2023 High

    C-terminal FGF23 fragments generated by FURIN cleavage in osteocytes were shown to have an independent biological function: binding and sequestering BMP2/BMP9 to suppress hepcidin production, thereby increasing iron availability during inflammation.

    Evidence Osteocyte-specific Fgf23-KO and Furin-KO mice, C-terminal FGF23 overexpression, BMP co-administration, hepcidin mRNA and serum iron measurements

    PMID:37053547

    Open questions at the time
    • Structural basis for C-terminal FGF23 binding to BMPs not resolved
    • Whether circulating C-terminal FGF23 fragments in CKD patients regulate hepcidin not confirmed in humans

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for FGFR4-mediated Klotho-independent cardiac signaling, whether C-terminal FGF23 fragments regulate iron metabolism in human CKD, how multiple transcriptional inputs (phosphate, 1,25D, insulin, inflammation, aldosterone, G-3-P) are integrated at the FGF23 promoter in osteocytes, and whether hepatic FGF23 undergoes the same post-translational processing as bone-derived FGF23.
  • No structure of FGFR4–FGF23 complex
  • Human validation of C-terminal FGF23 iron-regulatory function lacking
  • Quantitative model of FGF23 transcriptional regulation absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 6 R-HSA-382551 Transport of small molecules 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 1
Partners
ESRRGFAM20CFGFR1FGFR2FGFR4FURINGALNT3KL
Complex memberships
FGF23–FGFR1c–α-Klotho ternary complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 FGF23 was identified as a novel secreted protein (251 amino acids with a signal sequence) encoded by the FGF23 gene on chromosome 12p13, and missense mutations in FGF23 at the RXXR motif (R176Q, R179W, R179Q) were identified as causative for autosomal dominant hypophosphatemic rickets (ADHR), establishing FGF23 as the ADHR gene. Positional cloning, genomic sequencing, cDNA cloning, and expression studies in insect cells Nature genetics / Biochemical and biophysical research communications High 11032749 11062477
2001 Overproduction of FGF23 by tumors causes tumor-induced osteomalacia (TIO); recombinant FGF23 decreased serum phosphate in mice within 12 h; FGF23 undergoes proteolytic cleavage at the RXXR motif (between Arg179 and Ser180), and only the full-length protein is phosphaturic — N- and C-terminal fragments are not. Recombinant protein administration in mice, CHO cell implantation model, Western blot with site-specific antibodies Proceedings of the National Academy of Sciences of the United States of America High 11344269
2001 ADHR mutations (R176Q, R179W, R179Q) in the RXXR cleavage motif render FGF23 resistant to proteolytic cleavage, resulting in secretion of intact 32 kDa protein rather than processed fragments, explaining elevated circulating FGF23 in ADHR. Site-directed mutagenesis, transient transfection into HEK293 cells, Western blot with N- and C-terminal antibodies Kidney international High 11737582
2002 Mutant FGF23 (R179Q) resistant to proteolytic cleavage at Arg179-Ser180 induces hypophosphatemia in vivo, suppresses renal and intestinal Na/Pi co-transport activities and serum 1,25-dihydroxyvitamin D3 independently of PTH; native FGF23 is rapidly processed intracellularly and the intact form is required for phosphaturic activity. Naked DNA injection in animals, protein infusion in thyroparathyroidectomized rats, Na/Pi co-transport assays, Western blot The Journal of biological chemistry High 12130585 12419819
2003 FGF23 regulates phosphate homeostasis independently of PTH by reducing renal NaPi-2a (sodium-phosphate cotransporter) mRNA and protein, and suppresses 1,25(OH)2D by reducing renal 25-hydroxyvitamin D-1α-hydroxylase mRNA and increasing 24-hydroxylase mRNA; these effects precede hypophosphatemia and are reproduced in parathyroidectomized animals. Recombinant FGF23 injection in normal and parathyroidectomized rats, time-course analysis of serum and renal mRNA/protein Journal of bone and mineral research High 15040831
2003 PHEX does not directly cleave FGF23 (FGF23 is not a direct PHEX substrate), but inactivating PHEX mutations in Hyp mice cause a bone-restricted increase in fgf23 transcripts, indicating PHEX regulates FGF23 expression rather than its degradation. In vitro cleavage assays in COS-7 cells co-expressing PHEX and FGF23, real-time RT-PCR in Hyp mouse bone, osteoblast cultures The Journal of biological chemistry High 12874285
2004 Transgenic mice overexpressing wild-type human FGF23 under the collagen I promoter exhibit hypophosphatemia, increased urinary phosphate excretion, decreased renal Npt2a/Npt2c mRNA, reduced 1,25(OH)2D, and osteomalacia/rickets, phenocopying ADHR, TIO, and XLH. Transgenic mouse generation and phenotypic characterization including serum biochemistry, renal mRNA analysis, histology, bone densitometry Endocrinology High 14988389
2004 An FGF23 missense mutation (p.S71G) causing familial tumoral calcinosis results in retention of intact FGF23 protein in the Golgi complex and secretion of only the C-terminal fragment, demonstrating that intact FGF23 secretion is required for its phosphaturic activity and that loss of intact FGF23 causes hyperphosphatemia. Mutant FGF23 expression in HEK293 cells, Western blot, circulating FGF23 measurement in affected individual Human molecular genetics High 15590700
2005 FGF23-induced reductions in renal NaPi2a protein and 1α-hydroxylase mRNA are independent of the 1,25-dihydroxyvitamin D/vitamin D receptor (VDR) system, demonstrated in VDR-null mice; additionally, FGF23 production in bone is regulated by calcium via a VDR-independent mechanism, and dietary phosphate stimulation of FGF23 requires VDR. Recombinant FGF23 injection in VDR knockout mice, renal protein and mRNA analysis, dietary manipulation American journal of physiology. Renal physiology High 15998839
2006 Klotho converts FGF receptor 1c (FGFR1c) into a specific high-affinity receptor for FGF23 by binding both FGF23 and FGFR1c; forced expression of Klotho enables high-affinity FGF23 binding and restores cellular responsiveness to FGF23; anti-Klotho antibody injection induces FGF23 incompetence in vivo. Renal homogenate pull-down, forced Klotho expression in renal cell line, receptor binding assays, in vivo antibody injection Nature High 17086194
2006 Intact FGF23 secretion requires O-glycosylation; GalNAc-transferase T3 (GALNT3) selectively O-glycosylates FGF23 at a site within the RXXR subtilisin-like proprotein convertase recognition motif, blocking proteolytic processing and enabling secretion of intact, biologically active FGF23. Loss-of-function GALNT3 mutations cause familial tumoral calcinosis by preventing intact FGF23 secretion. Cell-based glycosylation and processing assays, mutagenesis, mass spectrometry of O-glycosylation sites The Journal of biological chemistry High 16638743
2006 FGF23 exhibits low affinity for all four FGF receptor splice variants (FGFR1-4) compared with paracrine FGFs, consistent with its endocrine mode of action requiring Klotho co-receptor for high-affinity signaling. BaF3 cell mitogenesis assays testing all 22 FGF family members against seven principal FGFRs The Journal of biological chemistry Medium 16597617
2007 FGF23 acts directly on the parathyroid gland: the parathyroid expresses Klotho and FGF receptors; FGF23 activates the MAPK/ERK1/2 pathway in parathyroid tissue, induces EGR1 expression, and suppresses PTH secretion and PTH gene expression; these effects are prevented by MAPK inhibitors. Recombinant FGF23 administration in rats, in vitro rat parathyroid cultures, MAPK inhibitor experiments, ERK1/2 phosphorylation assays The Journal of clinical investigation High 17992255
2007 C-terminal fragments of FGF23 beginning at residue 176-180 retain phosphaturic activity in rats (increasing fractional phosphate excretion), reducing serum phosphate and 1,25(OH)2D; further truncation to FGF23 206-251 abolishes activity; a 26-amino acid fragment (180-205) retains significant phosphaturic activity and reduces Na/Pi uptake in opossum kidney cells. Equimolar iv infusions in rats, opossum kidney cell Na/Pi uptake assays, Fgf23-/- mouse rescue experiments Pflugers Archiv : European journal of physiology Medium 17333246
2009 FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia predominantly via FGF receptor 1 (FGFR1); conditional FGFR1-knockout mice are completely unresponsive to FGF23-induced hypophosphatemia and NaPi reduction, whereas FGFR3- and FGFR4-knockout mice retain partial responsiveness. Conditional FGFR1-/- mice, FGFR3-/- and FGFR4-/- knockout mice, FGF23 injection, renal brush-border membrane protein analysis American journal of physiology. Renal physiology High 19515808
2009 The C-terminal tail of FGF23 (72 residues) mediates binding to a de novo site generated at the composite FGFR1c-Klotho interface; soluble ectodomains of FGFR1c and Klotho form a ternary complex with FGF23 in vitro; the isolated C-terminal tail peptide competitively inhibits FGF23 signaling and, when injected in vivo, induces hyperphosphatemia by blocking renal phosphate excretion. In vitro ternary complex reconstitution, competitive binding assays, in vivo injection in healthy rats and hypophosphatemic mouse models Proceedings of the National Academy of Sciences of the United States of America High 19966287
2010 Extracellular phosphate activates the Raf/MEK/ERK pathway via FGF receptors (FGFR1) in HEK293 cells, converging on FRS2α phosphorylation; this signaling requires the type III sodium/phosphate cotransporter PiT-1 as an upstream element, and overexpression of FGFR1 rescues reduced ERK phosphorylation in PiT-1 knockdown cells. FGFR1 knockdown/overexpression, PiT-1 knockdown, Western blot for phospho-ERK and phospho-FRS2α in HEK293 cells Journal of cellular biochemistry Medium 20717920
2011 FGF23 induces left ventricular hypertrophy via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway in cardiomyocytes; this effect is klotho-independent. Intramyocardial or intravenous FGF23 injection in wild-type mice causes LVH; klotho-deficient mice have elevated FGF23 and LVH; FGF receptor blockade in a CKD model attenuates LVH. Isolated rat cardiomyocyte hypertrophy assays, intramyocardial/intravenous FGF23 injection in mice, klotho-KO mouse model, CKD model with FGFR blocker, calcineurin-NFAT pathway analysis The Journal of clinical investigation High 21985788
2014 FGF23 directly regulates membrane abundance of the Na+:Cl- co-transporter NCC in distal renal tubules via a signaling mechanism involving the FGF receptor/αKlotho complex, ERK1/2, SGK1, and WNK4; gain of FGF23 function increases distal tubular NCC membrane expression, leading to sodium retention, volume expansion, hypertension, and cardiac hypertrophy in an αKlotho- and dietary Na+-dependent manner. Mouse models of Fgf23 and αKlotho deficiency, recombinant FGF23 injection, Hyp mice analysis, NCC inhibitor chlorothiazide rescue, co-transporter membrane fractionation EMBO molecular medicine High 24797667
2014 Loss of FGF-23 in mice results in increased hematopoietic stem cell frequency and increased erythropoiesis; administration of recombinant FGF-23 to wild-type mice rapidly decreases erythropoiesis; this effect is independent of elevated vitamin D levels in Fgf-23-/- mice, establishing FGF-23 as a negative regulator of erythropoiesis. Fgf-23-/- mice, recombinant FGF23 injection, flow cytometry of bone marrow and peripheral blood, fetal liver analysis The Journal of biological chemistry Medium 24509850
2015 FAM20C phosphorylates FGF23 post-translationally; this phosphorylation reduces FGF23 glycosylation and promotes its cleavage by proprotein convertases, thereby regulating the balance between intact (biologically active) and cleaved (inactive) FGF23. PC1/3 and PC2 (but not furin) efficiently cleave glycosylated FGF23 in vitro; PC5/6 expression increases markedly during osteoblast-to-osteocyte differentiation coinciding with increased FGF23 production. Radiolabeling of FGF23 in IDG-SW3 osteocyte-like cells, in vitro cleavage assays with recombinant convertases, qPCR and Western blot during cell differentiation Bone Medium 26746780
2015 The transcription factor EGR-1 mediates the hypophosphatemic effect of FGF23 downstream of ERK1/2 signaling: FGF23-induced hypophosphatemia and suppression of renal Npt2a/Npt2c are greatly blunted in egr-1-/- mice, while FGF23-mediated suppression of 1,25(OH)2D synthesis (cyp27b1 suppression/cyp24a1 induction) is preserved; ChIP-seq identifies EGR-1 binding sites near phosphate transport genes in kidney. FGF23 injection in egr-1-/- and Hyp/egr-1-/- mice, serum biochemistry, renal cotransporter mRNA, ChIP-sequencing for EGR-1 cistrome PloS one High 26588476
2015 Pro-inflammatory stimuli (TNF, IL-1β, TWEAK, LPS) up-regulate Fgf23 expression in osteocytes via NF-κB-dependent mechanisms; the same stimuli suppress negative regulators of FGF23 (Phex, Dmp1, Enpp1); GALNT3 (which protects FGF23 from furin cleavage) is increased, leading to elevated intact FGF23 secretion when furin is inhibited. IDG-SW3 osteocyte-like cell line, human bone samples, NF-κB inhibition, furin inhibition, qRT-PCR, ELISA for intact and C-terminal FGF23 Molecular and cellular endocrinology Medium 25458698
2015 1,25-dihydroxyvitamin D3 (1,25D) induces FGF23 expression in osteoblasts/osteocytes via a composite ETS1-VDR/Nurr1 cis-element in the FGF23 proximal promoter (-346 bp); mutation of either element reduces 1,25D-driven transcription; 1,25D represses FGF23 in adipocytes via the same region, indicating cell-type-specific transcription factor context switches the response. FGF23 promoter truncation-luciferase reporters in osteoblast and adipocyte cell lines, site-directed mutagenesis of cis-elements, high calcium challenge in osteoblasts The Journal of endocrinology Medium 26148725
2015 Phosphate stimulates FGF23 transcription in osteoblasts (UMR-106) via NADPH oxidase-induced reactive oxygen species (ROS) production and subsequent MEK-ERK pathway activation; sodium-phosphate cotransporter inhibition (phosphonoformic acid) and MEK inhibitor (PD98059) block this effect; phosphate does not affect Fgf23 mRNA stability. UMR-106 cell Fgf23 promoter-luciferase assays, ROS measurement (Fura-2/DCFH-DA), pharmacological inhibitors, mRNA stability assays Journal of bone and mineral metabolism Medium 25792238
2016 FGF23 inhibits neutrophil (PMN) recruitment by binding to FGFR2 on PMNs, activating protein kinase A (PKA), and thereby inhibiting Rap1 GTPase activation, which prevents selectin- and chemokine-triggered β2 integrin activation; PKA knockdown abolishes the inhibitory effect of FGF23 on integrin activation. Intravital microscopy in CKD mice, FGF23 neutralization, in vitro PMN adhesion/arrest/transendothelial migration assays, FGFR2 knockdown, PKA knockdown, Rap1 activation assays The Journal of clinical investigation High 26878171
2016 Aldosterone up-regulates Fgf23 transcription and secretion in osteoblastic cells via mineralocorticoid receptor activation, SGK1, NF-κB, and store-operated Ca2+ entry (SOCE) through Orai1; NF-κB-sensitive Orai1 expression mediates SOCE-dependent Fgf23 transcription; in vivo, DOCA treatment and salt depletion elevate serum C-terminal FGF23. UMR106 osteoblastic cells with pharmacological inhibitors (spironolactone, eplerenone, EMD638683, withaferin A, YM58483), Fura-2 Ca2+ measurement, qRT-PCR; DOCA-treated mice ELISA Biochemical and biophysical research communications / Journal of molecular medicine Medium 26631141 26773502
2017 Klotho expression in long bones (osteoblasts/osteocytes) is required for the induction of FGF23 production during renal failure via an autocrine feedback loop; mice with targeted deletion of Klotho in long bones fail to increase FGF23 expression in long bones (but not axial skeleton) during uremia, resulting in lower serum FGF23 and PTH and higher 1,25D; FGF23-treated bone cells require Klotho to increase FGF23 mRNA and ERK phosphorylation. Prx1-Cre;Klotho conditional KO mice with two renal failure models (adenine diet and 5/6 nephrectomy), FGF23 mRNA and protein analysis, primary osteoblast cultures with FGF23 treatment and ERK phosphorylation FASEB journal High 28183805
2018 Crystal structure of a 1:1:1 ternary complex of α-Klotho ectodomain, FGFR1c ligand-binding domain, and FGF23 reveals that α-Klotho simultaneously tethers FGFR1c via its D3 domain and FGF23 via its C-terminal tail, acting as a non-enzymatic scaffold that brings FGF23 and FGFR1c into proximity; heparan sulfate is still required for dimerization and receptor activation; the structure is incompatible with glycosidase activity of Klotho. X-ray crystallography of ternary complex, structure-function analysis Nature High 29342138
2018 Insulin and IGF1 suppress FGF23 production in osteoblasts via PI3K/PKB/Akt-mediated inhibition of the transcription factor FOXO1; insulin deficiency in mice causes a surge in serum FGF23 reversed by insulin administration; in women, FGF23 plasma concentration correlates negatively with insulin response to oral glucose load. UMR106 osteoblast-like cells with insulin/IGF1 treatment and PI3K/PKB inhibitors, streptozotocin-diabetic mice, FOXO1 inhibition, human oral glucose tolerance test correlation Proceedings of the National Academy of Sciences of the United States of America High 29760049
2018 FGF23 promotes hypertrophic growth of cardiac myocytes via FGFR4-dependent activation of phospholipase Cγ/calcineurin/NFAT signaling independent of klotho; this paracrine/autocrine mechanism contributes to cardiac fibrosis and LVH in CKD. Neonatal rat ventricular myocyte assays with recombinant FGF23, FGFR4-specific inhibitors, calcineurin-NFAT pathway analysis, immunohistochemistry in cardiac tissue Frontiers in endocrinology Medium 29892269
2019 FGF23-mediated activation of local renin-angiotensin-aldosterone system (RAAS) in cardiac myocytes and fibroblasts promotes hypertrophic growth and fibrosis; FGF23-induced cardiomyocyte hypertrophy via calcineurin/NFAT is attenuated by RAAS blockers (losartan, spironolactone) and cyclosporine A; FGF23 stimulates RAAS gene expression and induces angiotensin II production/secretion in cardiomyocytes. 5/6 nephrectomy rat model, neonatal rat ventricular myocyte and cardiac fibroblast cultures with recombinant FGF23, RAAS gene expression, losartan/spironolactone/cyclosporine A treatment International journal of molecular sciences Medium 31540546
2019 FGF23 and ATII share a common IP3-nuclear Ca2+-CaMKII-HDAC4 pathway for cardiomyocyte hypertrophy; FGF23 activates nuclear Ca2+-regulated CaMKII-HDAC4 signaling and induces IP3-triggered Ca2+ release from the nucleoplasmic Ca2+ store; FGF23-induced hypertrophy is attenuated by the ATII receptor antagonist losartan, and FGF23 increases intracellular ATII peptide and secretion in cardiomyocytes. Neonatal rat ventricular myocytes, Ca2+ imaging with Fura-2 and nuclear Ca2+ sensors, hypertrophy assays, ATII ELISA, losartan treatment Cellular and molecular life sciences Medium 30062428
2019 FGF23 induces atrial fibrosis via FGFR4 in cardiac fibroblasts by increasing ROS production and activating STAT3 and SMAD3 signaling; FGF23-stimulated STAT3 and SMAD3 interact physically; NAC (ROS inhibitor), SMAD3 inhibitor, and STAT3 inhibitor each reduce FGF23-induced pro-fibrotic factor expression. Cardiac fibroblast cultures from AF patients and controls, recombinant FGF23 treatment, ROS measurement, co-immunoprecipitation of STAT3-SMAD3, pathway inhibitors Journal of cellular physiology Medium 30953354
2020 Kidney-derived glycerol-3-phosphate (G-3-P) stimulates FGF23 production in bone via local GPAT-mediated lysophosphatidic acid (LPA) synthesis; this requires LPA receptor 1 (LPAR1). In acute kidney injury (AKI), circulating G-3-P increases rapidly and the AKI-induced rise in FGF23 is abrogated by GPAT inhibition or Lpar1 deletion. LC-MS metabolomics and aptamer proteomics of renal venous plasma, exogenous G-3-P and LPA administration in mice, GPAT inhibition, Lpar1-KO mice, AKI models The Journal of clinical investigation High 32065590
2021 FAM20C phosphorylates FGF23, targeting it for proteolysis by subtilisin-like proprotein convertase FURIN; O-glycosylation by GALNT3 prevents proteolysis, allowing secretion of biologically active intact FGF23; in the circulation, FGF23 may undergo further processing by plasminogen activators; canonical FGF23 signaling via KLOTHO-FGFR1c activates FRS2/RAS/RAF/MEK/ERK1/2. Synthesis of biochemical and genetic studies (review with cited experimental support) Journal of molecular endocrinology High 33338030
2021 ERR-γ (orphan nuclear receptor) in hepatocytes is induced by IL-6 (released during AKI) and drives ectopic hepatic FGF23 production; liver-specific ERR-γ deletion or ERR-γ inverse agonist treatment reduces hepatic FGF23 mRNA and plasma FGF23 in AKI mice; ectopic overexpression of ERR-γ alone is sufficient to induce hepatic FGF23. Folic acid-induced AKI mouse model, liver-specific ERR-γ KO mice, IL-6 neutralizing antibody, ERR-γ inverse agonist, hepatocyte-specific FGF23 KO, qPCR, ELISA Proceedings of the National Academy of Sciences of the United States of America High 33853949
2023 Bone-derived C-terminal FGF23 (Cter-FGF23) peptides, generated by FURIN-mediated cleavage of intact FGF23 in osteocytes, inhibit BMP2- and BMP9-induced hepcidin production by binding these BMPs, thereby increasing iron availability during acute inflammation; osteocyte-specific Fgf23 deletion or Furin deletion in osteocytes reduces Cter-FGF23 and causes excessive hepcidin production and iron deficiency in inflamed mice. Osteocyte-specific Fgf23-KO mice, osteocyte-specific Furin-KO mice, Cter-FGF23 overexpression mice, BMP2/BMP9 co-administration, hepcidin (Hamp) mRNA and serum iron measurement, Cter-FGF23 injection in inflamed Fgf23-KO mice Blood High 37053547
2024 In alcoholic liver disease, hepatic FGF23 expression is transcriptionally regulated by ERR-γ, which is activated downstream of CB1R (cannabinoid receptor 1) in response to alcohol; hepatocyte-specific FGF23 deletion reduces hepatic CYP2E1 expression and improves alcoholic liver disease by reducing oxidative stress and hepatocyte apoptosis, identifying a CB1R-ERR-γ-FGF23-CYP2E1 axis in ALD pathology. Hepatocyte-specific KO mice (CB1R-LKO, ERRγ-LKO, FGF23-LKO), alcohol-fed mouse model, ERRγ inverse agonist treatment, CYP2E1 expression analysis, apoptosis assays, oxidative stress measurements Redox biology Medium 38479224

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 FGF23 induces left ventricular hypertrophy. The Journal of clinical investigation 1599 21985788
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 1442 17086194
2003 FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1434 15040831
2000 Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nature genetics 1127 11062477
2001 Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proceedings of the National Academy of Sciences of the United States of America 1099 11344269
2006 Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. The Journal of biological chemistry 974 16597617
2011 Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney international 965 21389978
2011 Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 829 21673295
2007 The parathyroid is a target organ for FGF23 in rats. The Journal of clinical investigation 737 17992255
2009 Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 680 19414634
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney international 532 14633152
2010 Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annual review of medicine 500 20059333
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2000 Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochemical and biophysical research communications 422 11032749
2004 Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. The Journal of clinical endocrinology and metabolism 404 15613425
2001 Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney international 390 11737582
2003 Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. The Journal of biological chemistry 387 12874285
2018 α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling. Nature 385 29342138
2004 Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Endocrinology 380 14988389
2011 FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. Journal of the American Society of Nephrology : JASN 375 21903574
2010 The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Annals of internal medicine 363 20479029
2004 An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Human molecular genetics 361 15590700
2015 Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nature reviews. Drug discovery 357 26567701
2013 Fibroblast growth factor-23 and cardiovascular events in CKD. Journal of the American Society of Nephrology : JASN 355 24158986
2012 Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 352 22492635
2006 Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. The Journal of biological chemistry 345 16638743
2002 Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 343 12130585
2009 The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nature reviews. Endocrinology 340 19844248
2009 FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. American journal of physiology. Renal physiology 327 19515808
2013 Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 321 23505057
2009 Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proceedings of the National Academy of Sciences of the United States of America 319 19966287
2002 Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. The Journal of biological chemistry 317 12419819
2007 How fibroblast growth factor 23 works. Journal of the American Society of Nephrology : JASN 313 17494882
2005 Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. American journal of physiology. Renal physiology 279 15998839
2014 FGF23 regulates renal sodium handling and blood pressure. EMBO molecular medicine 255 24797667
2003 FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. American journal of physiology. Endocrinology and metabolism 250 12791601
2016 FGF23 signaling impairs neutrophil recruitment and host defense during CKD. The Journal of clinical investigation 228 26878171
2012 Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nature reviews. Endocrinology 218 22249518
2012 Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Experimental cell research 208 22421513
2013 Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism. Nature reviews. Nephrology 205 23774819
2004 Bone as a source of FGF23: regulation by phosphate? Bone 172 15542045
2018 FGF23 Actions on Target Tissues-With and Without Klotho. Frontiers in endocrinology 153 29770125
2016 Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease. Kidney diseases (Basel, Switzerland) 152 28785560
2014 Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli. Molecular and cellular endocrinology 145 25458698
2021 FGF23 signalling and physiology. Journal of molecular endocrinology 131 33338030
2011 Phosphate and FGF-23. Kidney international. Supplement 125 21346724
2009 Overview of the FGF23-Klotho axis. Pediatric nephrology (Berlin, Germany) 124 19626341
2014 FGF-23 is a negative regulator of prenatal and postnatal erythropoiesis. The Journal of biological chemistry 117 24509850
2012 Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway. Critical reviews in eukaryotic gene expression 112 22339660
2018 Insulin suppresses the production of fibroblast growth factor 23 (FGF23). Proceedings of the National Academy of Sciences of the United States of America 108 29760049
2020 Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney. The Journal of clinical investigation 107 32065590
2004 The wrickkened pathways of FGF23, MEPE and PHEX. Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists 102 15470265
2018 X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment. Endocrine reviews 99 29381780
2010 Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the FGF23/Klotho system. Clinical journal of the American Society of Nephrology : CJASN 98 20798257
2009 Novel regulators of Fgf23 expression and mineralization in Hyp bone. Molecular endocrinology (Baltimore, Md.) 97 19556340
2014 Osteocyte-specific deletion of Fgfr1 suppresses FGF23. PloS one 93 25089825
2012 Acute effects of very-low-protein diet on FGF23 levels: a randomized study. Clinical journal of the American Society of Nephrology : CJASN 90 22362063
2023 FGF23 and klotho at the intersection of kidney and cardiovascular disease. Nature reviews. Cardiology 88 37443358
2018 Paracrine Effects of FGF23 on the Heart. Frontiers in endocrinology 85 29892269
2016 Ironing out the cross talk between FGF23 and inflammation. American journal of physiology. Renal physiology 82 27582104
2019 FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis. International journal of molecular sciences 81 31540546
2016 Update on FGF23 and Klotho signaling. Molecular and cellular endocrinology 81 27178987
2017 FGF23 and Left Ventricular Hypertrophy in Children with CKD. Clinical journal of the American Society of Nephrology : CJASN 77 29025789
2013 Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor. PloS one 75 23967103
2012 The role of FGF23 in CKD--with or without Klotho. Nature reviews. Nephrology 75 22714041
2020 Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease. Toxins 74 32188018
2016 Up-regulation of FGF23 release by aldosterone. Biochemical and biophysical research communications 74 26773502
2023 Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions. Nature reviews. Nephrology 73 36624273
2010 Both FGF23 and extracellular phosphate activate Raf/MEK/ERK pathway via FGF receptors in HEK293 cells. Journal of cellular biochemistry 72 20717920
2015 Expression of Fgf23 in activated dendritic cells and macrophages in response to immunological stimuli in mice. Biological & pharmaceutical bulletin 69 25739891
2014 New insights into the FGF23-Klotho axis. Seminars in nephrology 67 25498378
2016 The FGF23 and Klotho system beyond mineral metabolism. Clinical and experimental nephrology 64 27838783
2008 PHEX, FGF23, DMP1 and beyond. Current opinion in nephrology and hypertension 64 18660670
2021 FGF23-related hypophosphatemic rickets/osteomalacia: diagnosis and new treatment. Journal of molecular endocrinology 60 33295878
2019 Physiology of FGF23 and overview of genetic diseases associated with renal phosphate wasting. Metabolism: clinical and experimental 60 30664852
2018 FGF23 in Cardiovascular Disease: Innocent Bystander or Active Mediator? Frontiers in endocrinology 60 30013515
2019 Regulation of fibroblast growth factor 23 (FGF23) in health and disease. FEBS letters 59 31199502
2012 The chicken or the egg: PHEX, FGF23 and SIBLINGs unscrambled. Cell biochemistry and function 52 22573484
2012 FGF-23 and the progression of coronary arterial calcification in patients new to dialysis. Clinical journal of the American Society of Nephrology : CJASN 52 22997345
2008 The discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis. Cellular and molecular life sciences : CMLS 51 18726073
2022 PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond. Frontiers in endocrinology 50 36246903
2018 Klotho-FGF23, Cardiovascular Disease, and Vascular Calcification: Black or White? Current vascular pharmacology 50 28294047
2018 Phosphate Homeostasis, Inflammation and the Regulation of FGF-23. Kidney & blood pressure research 50 30504710
2019 FGF23, Biomarker or Target? Toxins 48 30909513
2015 Phosphate enhances Fgf23 expression through reactive oxygen species in UMR-106 cells. Journal of bone and mineral metabolism 48 25792238
2015 NFκB-sensitive Orai1 expression in the regulation of FGF23 release. Journal of molecular medicine (Berlin, Germany) 47 26631141
2007 Biological activity of FGF-23 fragments. Pflugers Archiv : European journal of physiology 47 17333246
2020 Osteocytic FGF23 and Its Kidney Function. Frontiers in endocrinology 44 32982979
2022 The regulation of FGF23 under physiological and pathophysiological conditions. Pflugers Archiv : European journal of physiology 43 35084563
2019 FGF23, Hypophosphatemia, and Emerging Treatments. JBMR plus 43 31485552
2015 Posttranslational processing of FGF23 in osteocytes during the osteoblast to osteocyte transition. Bone 43 26746780
2011 Phosphate and FGF-23. Kidney international 42 26746858
2018 FGF23 beyond Phosphotropic Hormone. Trends in endocrinology and metabolism: TEM 40 30217676
2019 FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways. Journal of cellular physiology 39 30953354
2015 FGF23 is elevated in multiple myeloma and increases heparanase expression by tumor cells. Oncotarget 39 25944690
2020 Phosphate-sensing and regulatory mechanism of FGF23 production. Journal of endocrinological investigation 38 32140858
2018 Crosstalk between FGF23- and angiotensin II-mediated Ca2+ signaling in pathological cardiac hypertrophy. Cellular and molecular life sciences : CMLS 38 30062428
2017 Klotho expression in long bones regulates FGF23 production during renal failure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 28183805
2016 Extrarenal effects of FGF23. Pediatric nephrology (Berlin, Germany) 37 27704252
2021 Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer. Frontiers in cell and developmental biology 36 33520985
2018 FGF23C-tail improves diabetic nephropathy by attenuating renal fibrosis and inflammation. BMC biotechnology 36 29843712
2015 FGF23 gene regulation by 1,25-dihydroxyvitamin D: opposing effects in adipocytes and osteocytes. The Journal of endocrinology 36 26148725
2009 FGF-23 in bone biology. Pediatric nephrology (Berlin, Germany) 35 20012997
2023 Bone-derived C-terminal FGF23 cleaved peptides increase iron availability in acute inflammation. Blood 33 37053547
2017 Pleiotropic Actions of FGF23. Toxicologic pathology 33 29096595
2021 Regulation of FGF23: Beyond Bone. Current osteoporosis reports 32 34757587
2016 The FGF23/Klotho axis in the regulation of mineral and metabolic homeostasis. Hormone molecular biology and clinical investigation 32 26943611
2016 Fgf23 and parathyroid hormone signaling interact in kidney and bone. Molecular and cellular endocrinology 32 27498418
2019 The EPO-FGF23 Signaling Pathway in Erythroid Progenitor Cells: Opening a New Area of Research. Frontiers in physiology 31 30971944
2017 Klotho Lacks an FGF23-Independent Role in Mineral Homeostasis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 31 28600880
2013 Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. Contributions to nephrology 31 23652554
2024 ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress. Redox biology 30 38479224
2019 Cardiac FGF23: new insights into the role and function of FGF23 after acute myocardial infarction. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 29 30852297
2021 Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury. Proceedings of the National Academy of Sciences of the United States of America 28 33853949
2018 Phosphate control in reducing FGF23 levels in hemodialysis patients. PloS one 28 30086150
2020 Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23. Scientific reports 26 33057033
2019 Vitamin D sterols increase FGF23 expression by stimulating osteoblast and osteocyte maturation in CKD bone. Bone 26 31377240
2020 Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25 31968132
2015 Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule. PloS one 25 26588476
2012 Frequent expression of fibroblast growth factor-23 (FGF23) mRNA in aneurysmal bone cysts and chondromyxoid fibromas. Journal of clinical pathology 25 22933546
2019 αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight. Cellular and molecular life sciences : CMLS 24 31350618
2014 The P2Y13 receptor regulates phosphate metabolism and FGF-23 secretion with effects on skeletal development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 24487286
2020 Influence of FGF23 and Klotho on male reproduction: Systemic vs direct effects. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 32729975
2018 FGF23 and Fetuin-A Interaction in the Liver and in the Circulation. International journal of biological sciences 22 29904273
2022 Infigratinib Reduces Fibroblast Growth Factor 23 (FGF23) and Increases Blood Phosphate in Tumor-Induced Osteomalacia. JBMR plus 21 35991529
2016 The FGF23/KLOTHO Regulatory Network and Its Roles in Human Disorders. Vitamins and hormones 21 27125741
2022 Mouse liver injury induces hepatic macrophage FGF23 production. PloS one 20 35231062
2015 Hyperphosphatemic familial tumoral calcinosis: genetic models of deficient FGF23 action. Current osteoporosis reports 19 25656441