Inflammatory cytokines have a negative effect on myoblast differentiation

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Myoblast differentiation is a process that is required for the regeneration of myofibres post injury. In old age this is impaired and contributes to the onset of sarcopenia, and the resulting loss of muscle mass and strength.
A research paper published last week in Skeletal Muscle explores the effects of IL-1α and TNF-α on myotube differentiation, and the signalling cascades through which they act. Despite the ongoing debate into whether pro-inflammatory cytokines have a positive or negative effect on muscle cell differentiation, the results from this article clearly demonstrate the anti-differentiation effects of IL-1α and TNF-α.
Trendelenburg et al. show that human myoblasts treated with IL-1α and TNF-α induce Activin A de novo synthesis via the TAK-1/p38/NFκB pathway. TAK-1 and p38 are both required for Activin A induction – with the inhibition of TAK-1 blocking both the increase in Activin A and the downstream activation of p38, and the inhibition of p38 resulting in increased differentiation. NFκB also contributes to Activin A induction, though inhibition of NFκB is less effective than inhibition of p38 in rescuing myoblast differentiation. This induction of Activin A then results in the activation of downstream Activin receptor signalling via SMAD2/3 transcription factors, and the inhibition of myoblast differentiation.
This study establishes the mechanism for an additional anti-muscle effect of cytokines – the blockade of differentiation by Activin A secretion” explain the authors. “The induction of Activin A by TNF-α and IL-1α may help to explain some of the phenotypes previously reported in aging animals, including humans”.
Visit the Skeletal Muscle homepage to read the article in full.