TGF-beta1 favors the development of fast type identity during soleus muscle regeneration

J Muscle Res Cell Motil. 2006;27(1):1-8. doi: 10.1007/s10974-005-9014-9. Epub 2005 Dec 17.

Abstract

Transforming growth factor-beta1 (TGF-beta1) 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-beta1 or neutralizing TGF-beta1 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-beta1 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-beta1 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-beta1, it induced a shift to a less slow MHC phenotype and contractile characteristics. Conversely, neutralization of TGF-beta1 in the regenerating fast muscle induced a shift to a less fast MHC expression. Together these results suggest that TGF-beta1 influences some aspects of fast muscle-type patterning during skeletal muscle regeneration.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle Fibers, Fast-Twitch / cytology
  • Muscle Fibers, Fast-Twitch / drug effects
  • Muscle Fibers, Fast-Twitch / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Myosin Heavy Chains / drug effects
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Protein Isoforms / drug effects
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Wistar
  • Regeneration / drug effects
  • Regeneration / physiology*
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / metabolism
  • Toxins, Biological / pharmacology
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / pharmacology
  • Transforming Growth Factor beta1 / physiology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Antibodies
  • Protein Isoforms
  • Toxins, Biological
  • Transforming Growth Factor beta1
  • Myosin Heavy Chains