title: IGF-II is up-regulated and myofibres are hypertrophied in regenerating soleus of mice lacking FGF6.
abstract: Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the use of FGF6(-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remains largely unclear. Using FGF6(-/-) mice, we first analysed the morphology of the regenerated soleus following cardiotoxin injection and showed hypertrophied myofibres in soleus of the mutant mice as compared to wild-type mice. Secondly, to examine the function of the IGF family in the hypertrophy process, we used semiquantitative and real-time RT-PCR assays and Western blots to monitor the expression of the insulin-like growth factors (IGF-I and IGF-II), their receptors [type I IGF receptor (IGF1R) and IGF-II receptor (IGF2R)], and of a binding protein IGFBP-5 in regenerating soleus muscles of FGF6(-/-) knockout mice vs. wild-type mice. In the mutant, both IGF-II and IGF2R, but not IGF-I and IGF1R, were strongly up-regulated, whereas IGFBP5 was down-regulated, strongly suggesting that, in the absence of FGF6, the mechanisms leading to myofibre hypertrophy were mediated specifically by an IGF-II/IGF2R signalling pathway distinct from the classic mechanism involving IGF-I and IGF1R previously described for skeletal muscle hypertrophy. The potential regulating role of IGFBP5 on IGF-II expression is also discussed. This report shows for the first time a specific role for FGF6 in the regulation of myofibre size during a process of in vivo myogenesis.
authors.affiliation: UMR 7060 CNRS, Equipe Biologie du Développement et de la Différenciation Neuromusculaire, Centre Universitaire des Saints-Pères, Université René Descartes, F-75270, Paris Cedex 06, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Armand
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lécolle
authors.forename: Thierry
authors.initials: T
authors.lastname: Launay
authors.forename: Claude
authors.initials: C
authors.lastname: Pariset
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fiore
authors.forename: Bruno
authors.initials: B
authors.lastname: Della Gaspera
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Christophe
authors.initials: C
authors.lastname: Chanoine
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charbonnier
mesh_terms: D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics; D051522:Fibroblast Growth Factor 6; D005346:Fibroblast Growth Factors / Q000172:deficiency* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006984:Hypertrophy / Q000378:metabolism*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004179:Cobra Cardiotoxin Proteins; C486115:Fgf6 protein, mouse; D051522:Fibroblast Growth Factor 6; D018975:Insulin-Like Growth Factor Binding Protein 5; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1