<i>In Vivo</i> Electroporation Induces Cell Cycle Reentry of Myonuclei in Rat Skeletal Muscle

Abstract

ABSTRACT. Adult urodele amphibians such as newts are capable of regenerating lost structures including their limbs. In these species, dedifferentiation of myofiber is essential for the regenerative process. Upon terminal differentiation, nuclei of myofiber (myonuclei) are withdrawn from cell cycle, but prior to dedifferentiation, myonuclei reenter the cell cycle. In contrast with urodele amphibians, it is generally accepted that mammalian myofibers are not able to dedifferentiate in response to muscle injury. A recent study has suggested that electroporation can induce dedifferentiation response of skeletal muscle in newt limbs. In the present study, we examined whether myonuclei of skeletal muscle of mammals are capable of reentering the cell cycle by means of electroporation. Electroporation was applied to tibialis anterior muscle of the rat with or without plasmid DNA. Histological analyses revealed that, while electroporation induces degenerative/regenerative responses in skeletal muscle irrespective of the presence of plasmid DNA, the expression of proliferating cell nuclear antigen (PCNA) in myonuclei was observed only in the presence of plasmid DNA. The present results indicate that myonuclei of skeletal muscle are capable of reentering the cell cycle and suggest that in vivo electroporation can induce dedifferentiation of mammalian skeletal muscle.

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“…Although it is not typically used as a muscle regeneration model, it occurs here and we discuss our findings in this context (Collins et al 2007, Miyoshi et al 2012. A recent report shows that electroporation can induce myofibres to de-differentiate, which is of particular benefit to our model (Miyoshi et al 2012). In this report, DNA plasmids were active at least 7 days after electroporation (Miyoshi et al 2012), though the parameters of electroporation can affect DNA plasmid expression time and many vectors remain active for several weeks (Somiari et al 2000).…”

“…The method used to incorporate the DNA plasmids into the cell, electroporation, damages the muscle. Although it is not typically used as a muscle regeneration model, it occurs here and we discuss our findings in this context (Collins et al 2007, Miyoshi et al 2012. A recent report shows that electroporation can induce myofibres to de-differentiate, which is of particular benefit to our model (Miyoshi et al 2012).…”

“…, Miyoshi et al . ). A recent report shows that electroporation can induce myofibres to de‐differentiate, which is of particular benefit to our model (Miyoshi et al .…”

“…A recent report shows that electroporation can induce myofibres to de‐differentiate, which is of particular benefit to our model (Miyoshi et al . ). In this report, DNA plasmids were active at least 7 days after electroporation (Miyoshi et al .…”

“…In this report, DNA plasmids were active at least 7 days after electroporation (Miyoshi et al . ), though the parameters of electroporation can affect DNA plasmid expression time and many vectors remain active for several weeks (Somiari et al . ).…”