| First Author | Yaden BC | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 4 | Pages | 1152-66 |
| PubMed ID | 24655377 | Mgi Jnum | J:208124 |
| Mgi Id | MGI:5561146 | Doi | 10.1016/j.ajpath.2013.12.029 |
| Citation | Yaden BC, et al. (2014) Inhibition of activin a ameliorates skeletal muscle injury and rescues contractile properties by inducing efficient remodeling in female mice. Am J Pathol 184(4):1152-66 |
| abstractText | Activin A, a member of the transforming growth factor-beta superfamily, provides pleiotropic regulation of fibrosis and inflammation. We aimed at determining whether selective inhibition of activin A would provide a regenerative benefit. The introduction of activin A into normal muscle increased the expression of inflammatory and muscle atrophy genes Tnf, Tnfrsf12a, Trim63, and Fbxo32 by 3.5-, 10-, 2-, and 4-fold, respectively. The data indicate a sensitive response of muscle to activin A. Two hours after cardiotoxin-induced muscle damage, local activin A protein expression increased by threefold to ninefold. Neutralization of activin A with a specific monoclonal antibody in this muscle injury model decreased the muscle protein levels of lymphotoxin alpha and Il17a by 32% and 42%, respectively. Muscle histopathological features showed that activin A antibody-treated mice displayed an increase in muscle degradation, with the concomitant 9.2-fold elevation in F4/80-positive cells 3 days after injury. At the same time, the number of Pax7/Myod1-positive cells also increased, indicative of potentiated muscle precursor activation. Ultimately, activin A inhibition resulted in rapid recovery of muscle contractile properties indicated by a restoration of maximum and specific force. In summary, selective inhibition of activin A with a monoclonal antibody in muscle injury leads to the early onset of tissue degradation and subsequent enhanced myogenesis, thereby accelerating muscle repair and functional recovery. |
