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Immunobiology of ICAM-1 in Skeletal Muscle Growth Processes

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2014, Doctor of Philosophy, University of Toledo, Exercise Science.
Prior work in our laboratory demonstrated that ß2 integrins, adhesion molecules expressed exclusively by inflammatory cells, contribute to the hypertrophic response to muscle overload. A potential mechanism for ß2 integrin-mediated skeletal muscle hypertrophy involves its ligation to intercellular adhesion molecule-1 (ICAM-1), a major ligand for the ß2 integrin CD11b/CD18. We find ICAM-1 to be expressed by skeletal muscle cells (satellite cells/myoblasts and myofibers) following mechanical overload, and its expression augmented the ensuing muscle regenerative and hypertrophic responses, as indicated by increased formation of regenerating myofibers, as well as elevated levels of protein synthesis in the muscles of wild-type compared to ICAM-1-/- mice, respectively. These results are corroborated by findings from our cell culture model, which demonstrated that skeletal muscle cell expression of ICAM-1 expression augments critical events of myogenesis, specifically those pertaining to myoblast fusion and myotube hypertrophy. Furthemore, we identify the adhesive function of the ICAM-1 extracellular domain to mediate early events of myogenesis leading to the formation of nascent myotubes, whereas subsequent events of myotube hypertrophy occur through increased myonuclear number, rates of protein synthesis, and Akt/p70s6k signaling associated with the cytoplasmic domain of ICAM-1. Our collective findings demonstrate that ICAM-1 expression facilitates vital myogenic processes at multiple stages of skeletal muscle development and growth, and establish a novel role for adhesion molecules of the inflammatory response in regulating skeletal muscle growth processes.
Francis Pizza, Ph.D. (Committee Chair)
Thomas McLoughlin, Ph.D. (Committee Member)
Deborah Chadee, Ph.D. (Committee Member)
Phillip Gribble, Ph.D. (Committee Member)
123 p.

Recommended Citations

Citations

  • Goh, Q. (2014). Immunobiology of ICAM-1 in Skeletal Muscle Growth Processes [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404219785

    APA Style (7th edition)

  • Goh, Qingnian. Immunobiology of ICAM-1 in Skeletal Muscle Growth Processes. 2014. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404219785.

    MLA Style (8th edition)

  • Goh, Qingnian. "Immunobiology of ICAM-1 in Skeletal Muscle Growth Processes." Doctoral dissertation, University of Toledo, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404219785

    Chicago Manual of Style (17th edition)