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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.

SUBMITTER: Goh Q

PROVIDER: S-EPMC4323887 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.

Goh Qingnian Q Dearth Christopher L CL Corbett Jacob T JT Pierre Philippe P Chadee Deborah N DN Pizza Francis X FX

Experimental cell research 20140930 2

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 ...[more]

PMID: 25281303

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Project description:The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle.Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis.In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens ?1(I), ?2(I), ?1(III), and ?2(IV) as well as hydroxyproline. Alcohol also increased ?-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-? was detected. The mRNA and protein content for other ECM components, such as integrin-?5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-?3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-? and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle.These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms.

Project description:BackgroundFollowing systemic delivery, AAV9-mediated gene expression is significantly increased in ischemic versus non-ischemic muscle, suggesting that AAV9 is an attractive vector for treating peripheral arterial disease. Potential mechanisms underlying ischemia-augmented expression include: (i) increased vascular permeability and (ii) "unmasking" of endogenous AAV9 receptors. In the present study, we aimed to reconstitute the ischemic induction of AAV9 in vivo, using local injection of histamine (to increase vascular permeability) and neuraminidase (to desialylate cell surface glycans).MethodsBioassays were performed to optimize the effects of histamine and neuraminidase after intramuscular injection. Histamine and/or neuraminidase were then injected intramuscularly shortly before intravenous injection of an AAV9 vector expressing luciferase. Luciferase expression was serially assessed with bioluminescence imaging. At the end of the study, tissues were harvested for assays of luciferase activity and AAV9 genome copy number aiming to assess AAV-mediated gene expression and transduction, respectively.ResultsIntramuscular injection of either neuraminidase or neuraminidase plus histamine significantly increased both transduction and gene expression, whereas histamine alone had little effect. Pre-injection with neuraminidase increased AAV9-mediated gene delivery by four- to nine-fold and luciferase activity by 60-100-fold. Luciferase activity in neuraminidase-injected muscle was > 100-fold higher than in any off-target tissue (including heart, liver and brain).ConclusionsThe ischemic induction of AAV9-mediated gene expression in muscle can largely be reconstituted by pre-injecting neuraminidase intranmuscularly. This strategy may prove useful in future human gene therapy protocols as a quick and efficient means to selectively target systemically injected AAV9 to localized regions of muscle, thus decreasing the potential for adverse effects in off-target tissues.

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Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.

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Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.

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