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Antibody-Mediated Activation of FGFR1 Induces FGF23 Production and Hypophosphatemia
by
Chen, Mark Z.
, Carano, Richard A. D.
, Sonoda, Junichiro
, Gandham, Vineela D.
, Feng, Bo
, Wu, Ai-Luen
, Kolumam, Ganesh
, Zavala-Solorio, Jose
, Wyatt, Shelby K.
in
Activation
/ Animals
/ Antibodies
/ Base Sequence
/ Biocompatibility
/ Biology
/ Biomedical materials
/ Bo Feng
/ Bone Density
/ Cancer
/ Catabolism
/ Cell culture
/ Cells, Cultured
/ Cellular signal transduction
/ Cytochrome
/ Cytochrome P450
/ Cytochromes P450
/ DNA Primers
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Fibroblast growth factor 23
/ Fibroblast growth factor receptor 1
/ Fibroblast growth factor receptors
/ Fibroblast growth factors
/ Fibroblast Growth Factors - biosynthesis
/ Fibroblasts
/ Gene expression
/ Genetic aspects
/ Growth factors
/ Homeostasis
/ Hypophosphatemia
/ Hypophosphatemia - immunology
/ Kinases
/ Klotho protein
/ Ligands
/ Male
/ Medical imaging
/ Medical research
/ Medicine
/ Mice
/ Mice, Inbred C57BL
/ Mineralization
/ Molecular biology
/ Monoclonal antibodies
/ Mutation
/ Osteoblasts
/ Pathogenesis
/ Pharmacology
/ Phosphates
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 1 - immunology
/ Receptors
/ RNA
/ Rodents
/ siRNA
/ Sodium
/ Transduction
/ Vitamin D
2013
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Antibody-Mediated Activation of FGFR1 Induces FGF23 Production and Hypophosphatemia
by
Chen, Mark Z.
, Carano, Richard A. D.
, Sonoda, Junichiro
, Gandham, Vineela D.
, Feng, Bo
, Wu, Ai-Luen
, Kolumam, Ganesh
, Zavala-Solorio, Jose
, Wyatt, Shelby K.
in
Activation
/ Animals
/ Antibodies
/ Base Sequence
/ Biocompatibility
/ Biology
/ Biomedical materials
/ Bo Feng
/ Bone Density
/ Cancer
/ Catabolism
/ Cell culture
/ Cells, Cultured
/ Cellular signal transduction
/ Cytochrome
/ Cytochrome P450
/ Cytochromes P450
/ DNA Primers
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Fibroblast growth factor 23
/ Fibroblast growth factor receptor 1
/ Fibroblast growth factor receptors
/ Fibroblast growth factors
/ Fibroblast Growth Factors - biosynthesis
/ Fibroblasts
/ Gene expression
/ Genetic aspects
/ Growth factors
/ Homeostasis
/ Hypophosphatemia
/ Hypophosphatemia - immunology
/ Kinases
/ Klotho protein
/ Ligands
/ Male
/ Medical imaging
/ Medical research
/ Medicine
/ Mice
/ Mice, Inbred C57BL
/ Mineralization
/ Molecular biology
/ Monoclonal antibodies
/ Mutation
/ Osteoblasts
/ Pathogenesis
/ Pharmacology
/ Phosphates
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 1 - immunology
/ Receptors
/ RNA
/ Rodents
/ siRNA
/ Sodium
/ Transduction
/ Vitamin D
2013
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Antibody-Mediated Activation of FGFR1 Induces FGF23 Production and Hypophosphatemia
by
Chen, Mark Z.
, Carano, Richard A. D.
, Sonoda, Junichiro
, Gandham, Vineela D.
, Feng, Bo
, Wu, Ai-Luen
, Kolumam, Ganesh
, Zavala-Solorio, Jose
, Wyatt, Shelby K.
in
Activation
/ Animals
/ Antibodies
/ Base Sequence
/ Biocompatibility
/ Biology
/ Biomedical materials
/ Bo Feng
/ Bone Density
/ Cancer
/ Catabolism
/ Cell culture
/ Cells, Cultured
/ Cellular signal transduction
/ Cytochrome
/ Cytochrome P450
/ Cytochromes P450
/ DNA Primers
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Fibroblast growth factor 23
/ Fibroblast growth factor receptor 1
/ Fibroblast growth factor receptors
/ Fibroblast growth factors
/ Fibroblast Growth Factors - biosynthesis
/ Fibroblasts
/ Gene expression
/ Genetic aspects
/ Growth factors
/ Homeostasis
/ Hypophosphatemia
/ Hypophosphatemia - immunology
/ Kinases
/ Klotho protein
/ Ligands
/ Male
/ Medical imaging
/ Medical research
/ Medicine
/ Mice
/ Mice, Inbred C57BL
/ Mineralization
/ Molecular biology
/ Monoclonal antibodies
/ Mutation
/ Osteoblasts
/ Pathogenesis
/ Pharmacology
/ Phosphates
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 1 - immunology
/ Receptors
/ RNA
/ Rodents
/ siRNA
/ Sodium
/ Transduction
/ Vitamin D
2013
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Antibody-Mediated Activation of FGFR1 Induces FGF23 Production and Hypophosphatemia
Journal Article
Antibody-Mediated Activation of FGFR1 Induces FGF23 Production and Hypophosphatemia
2013
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Overview
The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) controls phosphate homeostasis by regulating renal expression of sodium-dependent phosphate co-transporters and cytochrome P450 enzymes involved in vitamin D catabolism. Multiple FGF Receptors (FGFRs) can act as receptors for FGF23 when bound by the co-receptor Klotho expressed in the renal tubular epithelium. FGFRs also regulate skeletal FGF23 secretion; ectopic FGFR activation is implicated in genetic conditions associated with FGF23 overproduction and hypophosphatemia. The identity of FGFRs that mediate the activity of FGF23 or that regulate skeletal FGF23 secretion remains ill defined. Here we report that pharmacological activation of FGFR1 with monoclonal anti-FGFR1 antibodies (R1MAb) in adult mice is sufficient to cause an elevation in serum FGF23 and mild hypophosphatemia. In cultured rat calvariae osteoblasts, R1MAb induces FGF23 mRNA expression and FGF23 protein secretion into the culture medium. In a cultured kidney epithelial cell line, R1MAb acts as a functional FGF23 mimetic and activates the FGF23 program. siRNA-mediated Fgfr1 knockdown induced the opposite effects. Taken together, our work reveals the central role of FGFR1 in the regulation of FGF23 production and signal transduction, and has implications in the pathogenesis of FGF23-related hypophosphatemic disorders.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Biology
/ Bo Feng
/ Cancer
/ Cellular signal transduction
/ Enzymes
/ Fibroblast growth factor receptor 1
/ Fibroblast growth factor receptors
/ Fibroblast Growth Factors - biosynthesis
/ Hypophosphatemia - immunology
/ Kinases
/ Ligands
/ Male
/ Medicine
/ Mice
/ Mutation
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 1 - immunology
/ RNA
/ Rodents
/ siRNA
/ Sodium
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