| First Author | Chen SE | Year | 2007 |
| Journal | Am J Physiol Cell Physiol | Volume | 292 |
| Issue | 5 | Pages | C1660-71 |
| PubMed ID | 17151142 | Mgi Jnum | J:125884 |
| Mgi Id | MGI:3760072 | Doi | 10.1152/ajpcell.00486.2006 |
| Citation | Chen SE, et al. (2007) TNF-alpha regulates myogenesis and muscle regeneration by activating p38 MAPK. Am J Physiol Cell Physiol 292(5):C1660-71 |
| abstractText | Although p38 MAPK activation is essential for myogenesis, the upstream signaling mechanism that activates p38 during myogenesis remains undefined. We recently reported that p38 activation, myogenesis, and regeneration in cardiotoxin-injured soleus muscle are impaired in TNF-alpha receptor double-knockout (p55(-/-)p75(-/-)) mice. To fully evaluate the role of TNF-alpha in myogenic activation of p38, we tried to determine whether p38 activation in differentiating myoblasts requires autocrine TNF-alpha, and whether forced activation of p38 rescues impaired myogenesis and regeneration in the p55(-/-)p75(-/-) soleus. We observed an increase of TNF-alpha release from C2C12 or mouse primary myoblasts placed in low-serum differentiation medium. A TNF-alpha-neutralizing antibody added to differentiation medium blocked p38 activation and suppressed differentiation markers myocyte enhancer factor (MEF)-2C, myogenin, p21, and myosin heavy chain in C2C12 myoblasts. Conversely, recombinant TNF-alpha added to differentiation medium stimulated myogenesis at 0.05 ng/ml while inhibited it at 0.5 and 5 ng/ml. In addition, differentiation medium-induced p38 activation and myogenesis were compromised in primary myoblasts prepared from p55(-/-)p75(-/-) mice. Increased TNF-alpha release was also seen in cardiotoxin-injured soleus over the course of regeneration. Forced activation of p38 via the constitutive activator of p38, MKK6bE, rescued impaired myogenesis and regeneration in the cardiotoxin-injured p55(-/-)p75(-/-) soleus. These results indicate that TNF-alpha regulates myogenesis and muscle regeneration as a key activator of p38. |
