title: Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.
abstract: We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle.
authors.affiliation: Department of Kinesiology, The University of Toledo, Toledo, OH, USA.
authors.forename: Qingnian
authors.initials: Q
authors.lastname: Goh
authors.affiliation: Department of Kinesiology, The University of Toledo, Toledo, OH, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Dearth
authors.affiliation: Department of Kinesiology, The University of Toledo, Toledo, OH, USA.
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Corbett
authors.affiliation: Centre d'Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille, France; INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille, France; CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
authors.affiliation: Department of Biological Sciences, The University of Toledo, Toledo, OH, USA.
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Chadee
authors.affiliation: Department of Kinesiology, The University of Toledo, Toledo, OH, USA. Electronic address: Francis.Pizza@utoledo.edu.
authors.forename: Francis X
authors.initials: FX
authors.lastname: Pizza
mesh_terms: D000818:Animals; D040881:CD11a Antigen / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D049109:Cell Proliferation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D040881:CD11a Antigen; D039481:CD11b Antigen; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Adhesion molecules; Inflammation; Muscle hypertrophy; Muscle regeneration