Abstract
FGF6, a member of the fibroblast growth factor (FGF) family, accumulated almost exclusively in the myogenic lineage, supporting the finding that FGF6 could specifically regulate myogenesis. Using FGF6 (-/-) mutant mice, important functions in muscle regeneration have been proposed for FGF6 but remain largely controversial. Here, we examined the effect of a single injection of recombinant FGF6 (rhFGF6) on the regeneration of mouse soleus subjected to cardiotoxin injection, specifically looking for molecular and morphological phenotypes. The injection of rhFGF6 has two effects. First, there is an up-regulation of cyclin D1 mRNA, accounting for the regulating role of a high FGF6 concentration on proliferation, and second, differentiation markers such as CdkIs and MHC I and Tn I increase and cellular differentiation is accelerated. We also show a down-regulation of endogenous FGF6, acceleration of FGFR1 receptor expression and deceleration of the FGFR4 receptor expression, possibly accounting for biphasic effects of exogenous FGF6 on muscle regeneration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cyclin D1 / genetics
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / drug effects
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Cyclins / metabolism
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DNA-Binding Proteins*
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Fibroblast Growth Factor 6
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Fibroblast Growth Factors / deficiency
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Fibroblast Growth Factors / genetics
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Fibroblast Growth Factors / pharmacology*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Genes, MHC Class I / drug effects
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Genes, MHC Class I / genetics
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Mice
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Mice, Inbred C3H
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Mice, Knockout
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Muscle Fibers, Skeletal / drug effects*
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Muscle Fibers, Skeletal / metabolism
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Muscle Proteins / drug effects
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Muscle Proteins / metabolism
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Muscle, Skeletal / drug effects*
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Muscle, Skeletal / growth & development*
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Muscle, Skeletal / metabolism
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MyoD Protein / drug effects
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MyoD Protein / metabolism
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Myogenic Regulatory Factor 5
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / pharmacology*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Reaction Time / drug effects
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Reaction Time / physiology
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Receptor Protein-Tyrosine Kinases / drug effects
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 4
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Receptors, Fibroblast Growth Factor / drug effects
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Receptors, Fibroblast Growth Factor / metabolism
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Regeneration / drug effects*
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Regeneration / physiology
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Trans-Activators*
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Troponin I / drug effects
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Troponin I / metabolism
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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Fgf6 protein, mouse
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Fibroblast Growth Factor 6
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Muscle Proteins
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Myf5 protein, mouse
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MyoD Protein
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Myogenic Regulatory Factor 5
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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Trans-Activators
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Troponin I
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Cyclin D1
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Fibroblast Growth Factors
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Fgfr1 protein, mouse
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Fgfr4 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 4