TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPK
- 1 May 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 292 (5) , C1660-C1671
- https://doi.org/10.1152/ajpcell.00486.2006
Abstract
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-α receptor double-knockout (p55−/−p75−/−) mice. To fully evaluate the role of TNF-α in myogenic activation of p38, we tried to determine whether p38 activation in differentiating myoblasts requires autocrine TNF-α, and whether forced activation of p38 rescues impaired myogenesis and regeneration in the p55−/−p75−/− soleus. We observed an increase of TNF-α release from C2C12 or mouse primary myoblasts placed in low-serum differentiation medium. A TNF-α-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-α 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-α 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-α regulates myogenesis and muscle regeneration as a key activator of p38.Keywords
This publication has 71 references indexed in Scilit:
- Role of TNF-α signaling in regeneration of cardiotoxin-injured muscleAmerican Journal of Physiology-Cell Physiology, 2005
- MyoD Targets Chromatin Remodeling Complexes to the Myogenin Locus Prior to Forming a Stable DNA-Bound ComplexMolecular and Cellular Biology, 2005
- Degradation of MyoD Mediated by the SCF (MAFbx) Ubiquitin LigaseJournal of Biological Chemistry, 2005
- Expression of myosin isoforms during notexin-induced regeneration of rat soleus musclesPublished by Elsevier ,2004
- A MyoD-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiationGenes & Development, 2004
- Amphoterin Stimulates Myogenesis and Counteracts the Antimyogenic Factors Basic Fibroblast Growth Factor and S100B via RAGE BindingMolecular and Cellular Biology, 2004
- Differential regulation of the phosphoinositide 3-kinase and MAP kinase pathways by hepatocyte growth factor vs. insulin-like growth factor-I in myogenic cellsExperimental Cell Research, 2004
- Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growthThe Journal of cell biology, 2003
- Tumor Necrosis Factor-α (TNF-α) Stimulates Chemotactic Response in Mouse Myogenic CellsCell Transplantation, 2003
- Transforming Growth Factor-β Inhibition of Insulin-like Growth Factor-binding Protein-5 Synthesis in Skeletal Muscle Cells Involves a c-Jun N-terminal Kinase-dependent PathwayPublished by Elsevier ,2001