IGF-II is up-regulated and myofibres are hypertrophied in regenerating soleus of mice lacking FGF6

• Published in: Experimental cell research Vol. 297; no. 1; pp. 27 - 38
• Main Authors: Armand, Anne-Sophie, Lécolle, Sylvie, Launay, Thierry, Pariset, Claude, Fiore, Frédéric, Della Gaspera, Bruno, Birnbaum, Daniel, Chanoine, Christophe, Charbonnier, Frédéric
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2004
• Subjects: Animals; Cobra Cardiotoxin Proteins - pharmacology; Down-Regulation - genetics; FGF6; Fibroblast Growth Factor 6; Fibroblast Growth Factors - deficiency; Fibroblast Growth Factors - genetics; Gene Expression Regulation, Developmental - genetics; Hypertrophy - metabolism; IGF, IGFR, growth factors; Insulin-Like Growth Factor Binding Protein 5 - genetics; Insulin-Like Growth Factor Binding Protein 5 - metabolism; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; Mice; Mice, Knockout; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle regeneration; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - genetics; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Receptor, IGF Type 2 - genetics; Receptor, IGF Type 2 - metabolism; Regeneration - genetics; RNA, Messenger - metabolism; Signal Transduction - genetics; Soleus; Up-Regulation - genetics; FGF6; Soleus; Muscle regeneration; IGF, IGFR, growth factors
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2004.02.021

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.