title: PKCε as a novel promoter of skeletal muscle differentiation and regeneration.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  This work identifies the PKCε-HMGA1 signaling axis as a positive regulator of skeletal muscle differentiation.
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy; Immune Cell Development and Host Defense, Research Institute of Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Di Marcantonio
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy; Centre for Molecular and Translational Oncology (COMT), University of Parma, Italy; Sport and Exercise Medicine Center (SEM), University of Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Galli
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Carubbi
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy; Centre for Molecular and Translational Oncology (COMT), University of Parma, Italy; Sport and Exercise Medicine Center (SEM), University of Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gobbi
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Queirolo
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Martini
authors.affiliation: Department of Medical Science, University of Ferrara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Merighi
authors.affiliation: Department of Human Sciences, Society and Health (HSSH), University of Cassino, FR, Italy; School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Vaccarezza
authors.affiliation: Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK; Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Surgery, Salerno, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Maffulli
authors.affiliation: Immune Cell Development and Host Defense, Research Institute of Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Sykes
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy; Centre for Molecular and Translational Oncology (COMT), University of Parma, Italy; Sport and Exercise Medicine Center (SEM), University of Parma, Italy. Electronic address: marco.vitale@unipr.it.
authors.forename: M
authors.initials: M
authors.lastname: Vitale
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Via Gramsci, 14, 43100 Parma, Italy; Centre for Molecular and Translational Oncology (COMT), University of Parma, Italy; Sport and Exercise Medicine Center (SEM), University of Parma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mirandola
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025741:HMGA1a Protein; D051744:Protein Kinase C-epsilon
keywords: C2C12; HMGA1; PKCε; Satellite cells; Skeletal muscle differentiation