ICAM‐1: a novel mechanism by which the inflammatory response augments myogenesis (1102.10)

Abstract

Recent investigations by our laboratory demonstrated that skeletal muscle cell expression of intercellular adhesion molecule‐1 (ICAM‐1), an important protein of the inflammatory response, augmented events of myogenesis in which myotubes are forming, adding nuclei, aligning, fusing, synthesizing proteins, and hypertrophying. Our current work extended these findings by incorporating pharmacological tools with an in vitro approach to discern underlying mechanisms associated with ICAM‐1 mediated myogenesis. Antibody neutralization revealed the extracellular domain of ICAM‐1 to be fundamentally important in augmenting homotypic adhesion of myoblasts, leading to myotube formation and myonuclear accretion. In contrast, inhibition of the cytoplasmic domain of ICAM‐1 with a cell permeable peptide revealed its critical role in augmenting both myotube formation and myonuclear accretion, as well as myotube alignment and fusion, rates of protein synthesis, and overall myotube size. Peptide inhibition further demonstrated that the signal transducing function of the ICAM‐1 cytoplasmic domain augmented events of myogenesis through mechanisms involving increased Rho GTPase (Rac1 and cdc42) and Akt/p70s6k activity. Taken together, our findings extend knowledge of the immunobiology of skeletal muscle cells by revealing a novel mechanism through which the inflammatory response facilitates myogenesis.Grant Funding Source: This research was supported by the ACSM Foundation Doctoral Student Research Grant(Q Goh)