PKCe 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...

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Main Authors: Di Marcantonio, D., Galli, D., Carubbi, C., Gobbi, G., Queirolo, V., Martini, S., Merighi, S., Vaccarezza, Mauro, Maffulli, N., Sykes, S., Vitale, M., Mirandola, P.
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/40273
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author Di Marcantonio, D.
Galli, D.
Carubbi, C.
Gobbi, G.
Queirolo, V.
Martini, S.
Merighi, S.
Vaccarezza, Mauro
Maffulli, N.
Sykes, S.
Vitale, M.
Mirandola, P.
author_facet Di Marcantonio, D.
Galli, D.
Carubbi, C.
Gobbi, G.
Queirolo, V.
Martini, S.
Merighi, S.
Vaccarezza, Mauro
Maffulli, N.
Sykes, S.
Vitale, M.
Mirandola, P.
author_sort Di Marcantonio, D.
building Curtin Institutional Repository
collection Online Access
description 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: PKCε 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 PKCε and HMGA1 in myogenic differentiation. Results: PKCε 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, PKCε accumulates in regenerating, centrally-nucleated myofibers. Pharmacological inhibition of PKCε 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.
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spelling curtin-20.500.11937-402732018-03-29T09:07:07Z PKCe as a novel promoter of skeletal muscle differentiation and regeneration Di Marcantonio, D. Galli, D. Carubbi, C. Gobbi, G. Queirolo, V. Martini, S. Merighi, S. Vaccarezza, Mauro Maffulli, N. Sykes, S. Vitale, M. Mirandola, P. 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: PKCε 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 PKCε and HMGA1 in myogenic differentiation. Results: PKCε 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, PKCε accumulates in regenerating, centrally-nucleated myofibers. Pharmacological inhibition of PKCε 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/40273 10.1016/j.yexcr.2015.09.017 restricted
spellingShingle Di Marcantonio, D.
Galli, D.
Carubbi, C.
Gobbi, G.
Queirolo, V.
Martini, S.
Merighi, S.
Vaccarezza, Mauro
Maffulli, N.
Sykes, S.
Vitale, M.
Mirandola, P.
PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title_full PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title_fullStr PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title_full_unstemmed PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title_short PKCe as a novel promoter of skeletal muscle differentiation and regeneration
title_sort pkce as a novel promoter of skeletal muscle differentiation and regeneration
url http://hdl.handle.net/20.500.11937/40273