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TNF-alpha regulates myogenesis and muscle regeneration by activating p38 MAPK

Shuen-Ei Chen1, Bingwen Jin, Yi-Ping Li

  • 1Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

American Journal of Physiology. Cell Physiology
|December 8, 2006
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) activates p38 mitogen-activated protein kinase (MAPK) for muscle development and regeneration. Blocking TNF-alpha impairs myogenesis, but forced p38 activation rescues these effects in mice.

Area of Science:

  • Muscle Biology
  • Cell Signaling
  • Immunology

Background:

  • p38 MAPK activation is crucial for myogenesis, but its upstream activators are unknown.
  • Previous studies showed impaired p38 activation, myogenesis, and regeneration in TNF-alpha receptor knockout mice.

Purpose of the Study:

  • To investigate the role of autocrine TNF-alpha in p38 activation during myogenesis.
  • To determine if forced p38 activation can rescue myogenesis and regeneration deficits in TNF-alpha receptor knockout mice.

Main Methods:

  • Assessed TNF-alpha release from differentiating myoblasts (C2C12 and primary mouse myoblasts).
  • Used TNF-alpha neutralizing antibodies and recombinant TNF-alpha to study its effects on myogenesis and p38 activation.
  • Utilized MKK6bE to constitutively activate p38 in knockout mice models.

Main Results:

  • Differentiating myoblasts release TNF-alpha, which is essential for p38 activation and expression of myogenic markers.
  • TNF-alpha receptor knockout myoblasts showed compromised p38 activation and myogenesis.
  • Forced p38 activation rescued myogenesis and regeneration in TNF-alpha receptor knockout mice.

Conclusions:

  • TNF-alpha acts as a key upstream activator of p38 during myogenesis and muscle regeneration.
  • Targeting the TNF-alpha/p38 pathway may offer therapeutic strategies for muscle repair.

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