Prostaglandin D2 inhibits C2C12 myogenesis.
Muscle repair following injury is preceded by a rapid inflammatory response with myoblasts being exposed to high levels of prostaglandin D(2) (PGD(2)) from invading leukocytes. We demonstrate that PGD(2) strongly inhibits C2C12 myogenesis as measured by cell fusion, creatine kinase activity and MyoD, myogenin and alpha-actin expression. Inhibition of myogenesis required micromolar PGD(2) concentrations and was independent of the known PGD(2) receptors DP1 and DP2. Unlike its cyclopentenone derivative 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), PGD(2) did not generate toxic mitochondrial superoxide indicating that the inhibition of myogenesis is not mediated by generation of high concentrations of PGD(2)-derived 15d-PGJ(2). Thus our observations provide evidence for a novel PGD(2) signalling mechanism during muscle repair exclusively mediated by high inflammatory associated PGD(2) concentrations. These findings indicate a complex interplay between myoblasts and inflammatory cells during the repair process and have implications for the use of non-steroidal anti-inflammatory drugs in the treatment of muscle injuries.
Veliça
Pedro
P
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK. velica@gmail.com
Khanim
Farhat L
FL
Bunce
Chris M
CM
D000818:Animals; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024510:Muscle Development / Q000187:drug effects* / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D013481:Superoxides; D003402:Creatine Kinase; D015230:Prostaglandin D2