AUTHOR=Corrick Katie L. , Stec Michael J. , Merritt Edward K. , Windham Samuel T. , Thomas Steven J. , Cross James M. , Bamman Marcas M. TITLE=Serum from human burn victims impairs myogenesis and protein synthesis in primary myoblasts JOURNAL=Frontiers in Physiology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2015.00184 DOI=10.3389/fphys.2015.00184 ISSN=1664-042X ABSTRACT=

The pathophysiological response to a severe burn injury involves a robust increase in circulating inflammatory/endocrine factors and a hypermetabolic state, both of which contribute to prolonged skeletal muscle atrophy. In order to characterize the role of circulating factors in muscle atrophy following a burn injury, human skeletal muscle satellite cells were grown in culture and differentiated to myoblasts/myotubes in media containing serum from burn patients or healthy, age, and sex-matched controls. While incubation in burn serum did not affect NFκB signaling, cells incubated in burn serum displayed a transient increase in STAT3 phosphorlyation (Tyr705) after 48 h of treatment with burn serum (≈ + 70%; P < 0.01), with these levels returning to normal by 96 h. Muscle cells differentiated in burn serum displayed reduced myogenic fusion signaling (phospho-STAT6 (Tyr641), ≈−75%; ADAM12, ≈-20%; both P < 0.01), and reduced levels of myogenin (≈−75%; P < 0.05). Concomitantly, myotubes differentiated in burn serum demonstrated impaired myogenesis (assessed by number of nuclei/myotube). Incubation in burn serum for 96 h did not increase proteolytic signaling (assessed via caspase-3 and ubiquitin levels), but reduced anabolic signaling [p-p70S6k (Ser421/Thr424), −30%; p-rpS6 (Ser240/244), ≈-50%] and impaired protein synthesis (−24%) (P < 0.05). This resulted in a loss of total protein content (−18%) and reduced cell size (−33%) (P < 0.05). Overall, incubation of human muscle cells in serum from burn patients results in impaired myogenesis and reduced myotube size, indicating that circulating factors may play a significant role in muscle loss and impaired muscle recovery following burn injury.