Injection of FGF6 accelerates regeneration of the soleus muscle in adult mice.
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.
Armand
Anne-Sophie
AS
Laboratoire de Biologie du Développement et de la Différenciation Neuromusculaire, LNRS UMR 7060, Centre Universitaire des Saints-Pères, Université René Descartes, 45 rue des Saints-Pères, F-75720 Paris Cedex 06, France.
Launay
Thierry
T
Pariset
Claude
C
Della Gaspera
Bruno
B
Charbonnier
Frédéric
F
Chanoine
Christophe
C
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D051522:Fibroblast Growth Factor 6; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005805:Genes, MHC Class I / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D017570:MyoD Protein / Q000187:drug effects / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D015534:Trans-Activators; D019210:Troponin I / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C486115:Fgf6 protein, mouse; D051522:Fibroblast Growth Factor 6; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D015534:Trans-Activators; D019210:Troponin I; D019938:Cyclin D1; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496372:Fgfr4 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051499:Receptor, Fibroblast Growth Factor, Type 4