TGF-β1 favors the development of fast type identity during soleus muscle regeneration
- First Online:
- 134 Downloads
Transforming growth factor-β1 (TGF-β1) is known to be expressed in the environment of developing fast muscle fibres during ontogenesis. In the present study, we have examined effects of administration of either TGF-β1 or neutralizing TGF-β1 antibody on the induction of fast type phenotype in regenerating skeletal muscles in rats. Expressions of fast and slow myosin heavy chain (MHC) isoforms were studied using protein electrophoresis, at 3 and 6 weeks after myotoxic treatment. Muscle contractile properties were also measured in situ. The results have shown that a single injection of TGF-β1 into the regenerating slow soleus muscle increased the expression of fast MHC-2x/d and MHC-2a and decreases that of slow MHC-1 (P<0.05). Moreover, it reduced the degree of tetanic fusion during contraction (P<0.05). Conversely, injection of neutralizing antibody against TGF-β1 into the regenerating fast EDL muscle increased the expression of MHC-2a and MHC-1 (P<0.05). In conclusion, when the slow muscle was regenerating in the presence of an increased level of TGF-β1, it induced a shift to a less slow MHC phenotype and contractile characteristics. Conversely, neutralization of TGF-β1 in the regenerating fast muscle induced a shift to a less fast MHC expression. Together these results suggest that TGF-β1 influences some aspects of fast muscle-type patterning during skeletal muscle regeneration.
- De Angelis L, Borghi S, Melchionna R, Berghella L, Baccarani-Contri M, Parise F, Ferrari S, Cossu G, (1998). Inhibition of myogenesis by transforming growth factor beta is density-dependent and related to the translocation of transcription factor MEF2 to the cytoplasmProc Natl Acad Sci USA 95: 12358–12363PubMedCrossRefGoogle Scholar
- Grifone R, Laclef C, Spitz F, Lopez S, Demignon J, Guidotti JE, Kawakami K, Xu PX, Kelly R, Petrof BJ, Daegelen D, Concordet JP, Maire P, (2004). Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotypeMol Cell Biol 24: 6253–6267PubMedCrossRefGoogle Scholar
- Snoj-Cvetko E, Sketelj J, Dolenc I, Obreza S, Janmot C, d’Albis A, Erzen I, (1996). Regenerated rat fast muscle transplanted to the slow muscle bed and innervated by the slow nerve, exhibits an identical myosin heavy chain repertoire to that of the slow muscleHistochem Cell Biol 106: 473–479PubMedCrossRefGoogle Scholar