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DISEASE MECHANISM

FAPs are sensors for skeletal myofibre atrophy

Nature Cell Biology volume 20, pages 864–865 (2018)Cite this article

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Skeletal muscle denervation leads to myofibre atrophy with fibrosis and fatty infiltration of muscle-resident fibroadipogenic progenitors (FAPs). A study shows that on denervation, FAPs activate pathogenic STAT3–IL-6 signalling. Inhibition of this pathway prevents atrophy and points to potential therapeutic targets.

Tissue regeneration is an essential response to injury and requires activation of local progenitor stem cells1. In skeletal muscle, terminally differentiated multinucleate myofibres are incapable of significant repair and are typically lost following physical trauma1. Skeletal muscle regeneration has been shown to rely principally on the satellite stem cell that resides adjacent to the myofibre in a quiescent state1. Injury stimulates satellite cell re-entry into the cell cycle, followed by a round of expansion and subsequent fusion into terminally differentiated myofibres2. Whereas the satellite cell is the stem cell that replaces damaged muscle, regeneration also depends on the function of non-myogenic progenitors that reside in the muscle interstitium3,4. Regulation of a stromal cell population that possesses both fibrogenic and adipogenic cell fate potentials, named fibroadipogenic cells or fibroadipogenic progenitors (FAPs)5,6, underlies the progression of myopathies and ageing — during which fibrotic cells accumulate with fatty infiltration, leading to compromised muscle function7. In this issue of Nature Cell Biology, Puri and colleagues describe a previously unrecognized role for FAPs as mediators of skeletal muscle atrophy in response to denervation8.

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Fig. 1: Schematic representation of a signalling role for FAPs in response to denervation.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM), UMR970, Paris, France

    Giovanna Marazzi & David Sassoon

  2. Cardiovascular Research Center (PARCC), Paris, France

    Giovanna Marazzi & David Sassoon

Authors
  1. Giovanna Marazzi
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  2. David Sassoon
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Correspondence to David Sassoon.

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The authors declare no competing interests.

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Marazzi, G., Sassoon, D. FAPs are sensors for skeletal myofibre atrophy. Nat Cell Biol 20, 864–865 (2018). https://doi.org/10.1038/s41556-018-0149-5

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  • DOI: https://doi.org/10.1038/s41556-018-0149-5

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