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Fibroblast Growth Factors, Second Edition systematically introduces readers to FGF in the fields of injury repair and regeneration, endocrinology and metabolism, structure and modification, pharmaceutics, pharmacology, FGF/FGFR inhibitor, engineering and new drug development. Fibroblast growth factors (FGFs) are secreted protein ligands that act in a paracrine or endocrine fashion to carry out their pleiotropic functions in development, tissue homeostasis and metabolism. This book covers the work from Li's team from 2013 to 2018 and will be a primer for scientists, particularly young students entering the FGFs field with an eye on basic research and application.
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Fibroblast growth factors. --- Fibroblast growth factor --- Growth factors --- Mitogens
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The main objective of the study was to investigate the role of growth factors, such as PDGF and FGF, in the regulation of gene expression. Both growth factors are involved in several biological processes such as cell growth, proliferation and differentiation, but are also implicated in diseases like cancer.
During the study, we examined the role played by PDGF-BB and by FGF2 on gene expression regulation in human fibroblasts, using a micro-array approach. Analyzing our micro-array data, we observed that PDGF-BB and FGF2 do not regulate gene expression in the same manner.
According to our micro-array results, 16 genes are specifically induced by PDGF-BB, 3 genes are specifically induced by FGF2 and a set of 22 genes is induced both by PDGF-BB and by FGF2. We also sought to explore the molecular mechanisms by witch PDGF and FGF induce gene transcription in fibroblast. Using immuno-precipitation and western-blot approaches, we explored different signalling pathways. We observed that the PI-3 kinase-STAT-PLCγl pathways are only activated by PDGF. On the other hand, we found that both PDGF and FGF induce activation of MAP kinases.
Using Ly294002, a PI-3 kinase inhibitor, we compared Ly294002 + PDGF-BB versus PDGF-BB by micro-array. We observed that 17 genes induced by PDGF-BB are down-regulated in the presence of Ly294002. Among these Bcl3, CISH, IRF-1, IFIT3, SOCS3 and FOS are all known targets of STAT transcription factors.
In order to understand whether there is any link between the PI-3 kinase and STAT pathways, we investigated the molecular mechanism by which PDGF activate the STAT pathways. We have demonstrated that PDGF stimulates STAT phosphorylation, both on tyrosine and on serine residues in a PI-3kinase independent manner. Using different signal transduction inhibitors, we observed that PDGF stimulates STAT3 phosphorylation on serine 727 thought the MAP kinases pathways. In addition, we have also investigated the role played both by PDGF and by FGF on SREBP activation, and observed that PDGF activates SREBP through the PI-3 kinase pathways.
IN conclusion, we suggest that the activation of PI-3 kinase is a critical difference between PDGF and FGF in human fibroblast L’objectif principal de ce mémoire était d’étudier le rôle des facteurs de croissance, tels que le PDGF et le FGF, dans le processus de régulation de l’expression des gènes. Les 2 facteurs de croissance exercent leurs effets cellulaires via l’activation des récepteurs à activité de tyrosine kinase. Les récepteurs PDGF et FGF sont responsables de plusieurs processus biologiques, notamment la croissance cellulaire, la prolifération ainsi que la différenciation cellulaire. Ils sont également impliquées dans certaines pathologies graves telles que le cancer.
Au cours de ce mémoire, nous avons utilisé la technique du micro-array pour étudier le rôle joué par le PDGF-BB et par le FGF2 dans la régulation de l’expression des gènes dans les fibroblastes humaines normaux. Les analyses de micro-array nous ont permis de démontrer que le PDGF-BB et le FGF2 ne régulent pas l’expression des mêmes gènes. D’après les résultats de nos études,16 gènes sont spécifiquement induits par le PDGF-BB, 3 gènes sont spécifiquement induits par le FGF2, et 22 gènes sont induits par le PDGF-BB ainsi que le FGF2.
Afin de mieux comprendre par lesquelles le PDGF et le FGF induisent la transcription des gènes dans les fibroblastes, nous avons utilisé les techniques de western-blot et d’immuno-précipitation pour explorer les différentes voies de transduction du signal. Nous avons constaté que seul le PDGF active les voies : PI 3 Kinase, STAT, et PLCγl, et que le PDGF et le FGF activent la voies des MAP kinases.
L’étude de l’expression des gènes par micro-array en utilisant le Ly294002, un inhibiteur de le PI-3 kinase nous a permis de comparer le Ly294002+PDGF-BB versus PDGF-BB. Nous avons observé que 17 gènes induits par le PDGF-BB sont inhibés par le Ly294002. Parmi ces gènes, il y a BCL-3, CISH, IRF-1, IFIT3, SOCS3 et FOS qui sont des cibles connues des facteurs de transcription STAT.
Dans le but de vérifier s’il y a un lien entre le voie PI-3 kinase et le voie STAT, nous avons étudié le mécanisme par lequel le PDGF active la voie STAT. Nous avons pu démonter que le PDGF stimule la phosphorylation des STAT sur les résidus tyrosines et sur les sérines, ce indépendamment de la voie PI-3 kinase. En utilisant différents inhibiteurs de voies de transduction du signal, nous avons découvert que le PDGF stimule la phosphorylation de la sérine 727 de STAT3 via la voie de MAP Kinases.
nous avons également étudié l’effet du PDGF et celui du FGF sur l’activation des facteurs de transcription SREBP, et nos analyses ont révélé que le PDGF active SREBP via la PI-3 Kinase.
En conclusion, nous suggérons que la voie PI-3 Kinase est le point de différence critique entre le PDGF et le FGF dans les fibroblastes humains
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Fibroblast Growth Factors. --- DNA Synthesis Factor --- Fibroblast Growth Factor --- Fibroblast Growth Regulatory Factor --- Growth Factor, Fibroblast --- Growth Factors, Fibroblast --- Fibroblast growth factors --- Congresses. --- congresses. --- Fibroblast Growth Factors --- Fibroblast growth factor --- Growth factors --- Mitogens --- Congresses --- Fibroblast growth factors - Congresses. --- FIBROBLAST GROWTH FACTOR --- CONGRESSES
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The fibroblast growth factors (FGFs) represent one of the relatively few families of extracellular signalling peptides that have been shown in recent decades to be key regulators of metazoan development. FGFs are required for multiple processes in both protostome and deuterostome groups. Given the wide range of regulatory roles attributed to the FGFs, it is perhaps not surprising that misregulation of this signalling pathway has been implicated in a number of human disease conditions. The focus of the present review is to look at the fundamental components of the FGF pathway and illustrate how this highly conserved regulatory cassette has been deployed to regulate multiple, diverse processes during vertebrate development. This review will explore examples from several vertebrate model organisms and include discussions of the role of FGF signalling in regulating the establishment of the mesoderm, neural patterning, morphogenesis, myogenesis, limb development, and the establishment of right-left asymmetry.
Fibroblast growth factors. --- Vertebrates -- Development. --- Vertebrates -- Growth & development. --- Fibroblast Growth Factors --- Chordata --- Intercellular Signaling Peptides and Proteins --- Animals --- Biological Factors --- Proteins --- Eukaryota --- Peptides --- Amino Acids, Peptides, and Proteins --- Organisms --- Chemicals and Drugs --- Fibroblast Growth Factor 1 --- Vertebrates --- Zoology --- Human Anatomy & Physiology --- Health & Biological Sciences --- Animal Biochemistry --- Animal Anatomy & Embryology --- Growth factors. --- Growth. --- Fibroblast Growth Factors. --- growth & development. --- Fibroblast growth factor --- Mesoderm --- Neurectoderm --- Xenopus --- Organogenesis --- Somites --- Limb --- MyoD --- Somitogenesis --- Morphogenesis --- Left-right asymmetry --- MAPK --- Sprouty --- ERK --- Map kinase phosphatase --- Signal transduction
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Facteurs de croissance nerveux --- Nerfs--Facteurs de croissance --- Nerve growth factor --- Zenuwen--Groeifactoren --- Fibroblast Growth Factors. --- Nerve Growth Factors --- Physiology --- Physiology.
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Fibroblast growth factors (FGFs) have been recognized primarily as autocrine/paracrine factors that regulate embryonic development and organogenesis. However, recent studies have revealed that some FGFs function as endocrine factors and regulate various metabolic processes in adulthood. Such FGFs, collectively called endocrine FGFs, are comprised of three members (FGF15/19, FGF21, and FGF23: FGF15 is the mouse ortholog of human FGF19). These endocrine FGFs share a common structural feature that enables the endocrine mode of action at the expense of the affinity to FGF receptors. To restore the affinity to FGF receptors in their target organs, the endocrine FGFs have designated the Klotho family of transmembrane proteins as obligate co-receptors. By expressing Klothos in a tissue-specific manner, this unique co-receptor system also enables the endocrine FGFs to specify their target organs among many tissues that express FGF receptors.
Endocrine toxicology. --- Fibroblast growth factors. --- Protein binding. --- Receptors, Growth Factor --- Anatomy --- Glycoside Hydrolases --- Intercellular Signaling Peptides and Proteins --- Metabolic Phenomena --- Peptides --- Proteins --- Receptors, Peptide --- Biological Factors --- Hydrolases --- Phenomena and Processes --- Enzymes --- Amino Acids, Peptides, and Proteins --- Receptors, Cell Surface --- Chemicals and Drugs --- Membrane Proteins --- Enzymes and Coenzymes --- Metabolism --- Receptors, Fibroblast Growth Factor --- Fibroblast Growth Factors --- Endocrine System --- Glucuronidase --- Biology --- Human Anatomy & Physiology --- Health & Biological Sciences --- Cytology --- Animal Biochemistry --- Fibroblast growth factors --- Endocrinology. --- Endocrine aspects. --- Metabolism. --- Fibroblast growth factor --- Life sciences. --- Gene expression. --- Cell biology. --- Life Sciences. --- Cell Biology. --- Gene Expression. --- Cell biology --- Cellular biology --- Cells --- Cytologists --- Genes --- Genetic regulation --- Biosciences --- Sciences, Life --- Science --- Expression --- Growth factors --- Mitogens --- Internal medicine --- Hormones --- Cytology.
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Fibroblast growth factors. --- Receptors, Fibroblast Growth Factor. --- Fibroblast Growth Factor 2. --- Cartilage-Derived Growth Factor --- Class II Heparin-Binding Growth Factor --- FGF-2 --- FGF2 --- Fibroblast Growth Factor-2 --- Heparin-Binding Growth Factor Class II --- Prostate Epithelial Cell Growth Factor --- Prostatropin --- Basic Fibroblast Growth Factor --- Fibroblast Growth Factor, Basic --- HBGF-2 --- Cartilage Derived Growth Factor --- FGF 2 --- FGF Receptor --- Fibroblast Growth Factor Receptor --- Heparin-Binding Growth Factor Receptor --- FGF Receptors --- Fibroblast Growth Factor Receptors --- Receptors, FGF --- Heparin Binding Growth Factor Receptor --- Receptor, FGF --- Fibroblast Growth Factors --- Fibroblast growth factor --- Growth factors --- Mitogens
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