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First published online 30 January 2007
doi: 10.1242/jcs.03372

Journal of Cell Science 120, 692-701 (2007)
Published by The Company of Biologists 2007
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Research Article

TACE release of TNF-{alpha} mediates mechanotransduction-induced activation of p38 MAPK and myogenesis

Mei Zhan1,*, Bingwen Jin1,*, Shuen-Ei Chen1, James M. Reecy2 and Yi-Ping Li1,{ddagger}

1 Department of Medicine, Baylor College of Medicine, One Baylor Plaza-520B, Houston, TX 77030, USA
2 Department of Animal Science, Iowa State University, Ames, IA 50011, USA

{ddagger} Author for correspondence (e-mail: yiping{at}bcm.tmc.edu)

Accepted 7 December 2006

Skeletal muscle responds to mechanical stimulation by activating p38 MAPK, a key signal for myogenesis. However, the mechanotransduction mechanism that activates p38 is unknown. Here we show that mechanical stimulation of myoblasts activates p38 and myogenesis through stimulating TNF-{alpha} release by TNF-{alpha} converting enzyme (TACE). In C2C12 or mouse primary myoblasts cultured in growth medium, static stretch activated p38 along with ERK1/2, JNK and AKT. Disrupting TNF-{alpha} signaling by TNF-{alpha}-neutralizing antibody or knocking out TNF-{alpha} receptors blocked stretch activation of p38, but not ERK1/2, JNK or AKT. Stretch also activated differentiation markers MEF2C, myogenin, p21 and myosin heavy chain in a TNF-{alpha}- and p38-dependent manner. Stretch stimulated the cleavage activity of TACE. Conversely, TACE inhibitor TAPI or TACE siRNA abolished stretch activation of p38. In addition, conditioned medium from stretched myoblast cultures activated p38 in unstretched myoblasts, which required TACE activity in the donor myoblasts, and TNF-{alpha} receptors in the recipient myoblasts. These results indicate that posttranscriptional activation of TACE mediates the mechanotransduction that activates p38-dependent myogenesis via the release of TNF-{alpha}.

Key words: Stretch, Myogenesis, p38 MAPK, TACE, TNF-{alpha}






© The Company of Biologists Ltd 2007