Cyclic Mechanical Stretch Stimulates the Proliferation of C2C12 Myoblasts and Inhibits Their Differentiation via Prolonged Activation of p38 MAPK

  • Kook, Sung-Ho (Institute of Oral Biosciences, Chonbuk National University) ;
  • Lee, Hyun-Jeong (National Livestock Research Institute, Rural Development Administration) ;
  • Chung, Wan-Tae (National Livestock Research Institute, Rural Development Administration) ;
  • Hwang, In-Ho (Department of Animal Resources and Biotechnology, Chonbuk National University) ;
  • Lee, Seung-Ah (Research Center of Bioactive Materials, Chonbuk National University) ;
  • Kim, Beom-Soo (Daewon Foreign Language High School) ;
  • Lee, Jeong-Chae (Institute of Oral Biosciences, Chonbuk National University)
  • 투고 : 2007.08.29
  • 심사 : 2008.02.11
  • 발행 : 2008.06.30

초록

Mitogen-activated protein kinases (MAPKs) play an indispensable role in activation of the myogenic program, which is responsive to mechanical stimulation. Although there is accumulating evidence of mechanical force-mediated cellular responses, the role of MAPK in regulating the myogenic process in myoblasts exposed to cyclic stretch is unclear. Cyclic stretch induced the proliferation of C2C12 myoblasts and inhibited their differentiation into myotubes. In particular, it induced persistent phosphorylation of p38 kinase, and decreased the level of phosphorylation of extracellular-signal regulated kinase (ERK). Partial inhibition of p38 phosphorylation increased cellular levels of MyoD and p-ERK in stretched C2C12 cells, along with increased myotube formation. Treatment with $10{\mu}M$ PD98059 prevented myogenin expression in response to a low dose of SB203580 ($3{\mu}M$) in the stretched cells, suggesting that adequate ERK activation is also needed to allow the cells to differentiate into myotubes. These results suggest that cyclic stretch inhibits the myogenic differentiation of C2C12 cells by activating p38-mediated signaling and inhibiting ERK phosphorylation. We conclude that p38 kinase, not ERK, is the upstream signal transducer regulating cellular responses to mechanical stretch in skeletal muscle cells.

키워드

참고문헌

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