PKCε as a novel promoter of skeletal muscle differentiation and regeneration

Introduction: Satellite cells are muscle resident stem cells and are responsible for
muscle regeneration. In this study we investigate the involvement of PKCε during muscle
stem cell differentiation in vitro and in vivo. Here, we describe the identification of a
previously unrecognized role for the PKCε – HMGA1 signaling axis in myoblast
differentiation and regeneration processes.
Methods: PKC expression was modulated in the C2C12 cell line and primary murine
satellite cells in vitro, as well as in an in vivo model of muscle regeneration.
Immunohistochemistry and immunofluorescence, RT-PCR and shRNA silencing techniques
were used to determine the role of PKC and HMGA1 in myogenic differentiation.
Results: PKC expression increases and subsequently re-localizes to the nucleus
during skeletal muscle cell differentiation. In the nucleus, PKCε blocks Hmga1 expression to
promote Myogenin and Mrf4 accumulation and myoblast formation. Following in vivo
muscle injury, PKC accumulates in regenerating, centrally-nucleated myofibers.
Pharmacological inhibition of PKC impairs the expression of two crucial markers of
muscle differentiation, namely MyoD and Myogenin, during injury induced muscle
regeneration.
Conclusion: This work identifies the PKCε – HMGA1 signaling axis as a positive
regulator of skeletal muscle differentiation.