Thrown for a loop: fibro-adipogenic progenitors in skeletal muscle fibrosis

Fibro-adipogenic progenitors (FAPs) are key regulators of skeletal muscle regeneration and homeostasis. However, dysregulation of these cells leads to fibro-fatty infiltration across various muscle diseases. FAPs are the key source of extracellular matrix (ECM) deposition in muscle, and disruption t...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2023-10, Vol.325 (4), p.C895-C906
Main Authors: Loomis, Taryn, Smith, Lucas R
Format: Article
Language:English
Subjects:
Adipocytes - pathology
Adipogenesis
Cell Differentiation - physiology
Extracellular matrix
Fibrosis
Homeostasis
Humans
Muscle contraction
Muscle, Skeletal - pathology
Musculoskeletal diseases
Phenotypes
Skeletal muscle
Stem Cells
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Summary:Fibro-adipogenic progenitors (FAPs) are key regulators of skeletal muscle regeneration and homeostasis. However, dysregulation of these cells leads to fibro-fatty infiltration across various muscle diseases. FAPs are the key source of extracellular matrix (ECM) deposition in muscle, and disruption to this process leads to a pathological accumulation of ECM, known as fibrosis. The replacement of contractile tissue with fibrotic ECM functionally impairs the muscle and increases muscle stiffness. FAPs and fibrotic muscle form a progressively degenerative feedback loop where, as a muscle becomes fibrotic, it induces a fibrotic FAP phenotype leading to further development of fibrosis. In this review, we summarize FAPs' role in fibrosis in terms of their activation, heterogeneity, contributions to fibrotic degeneration, and role across musculoskeletal diseases. We also discuss current research on potential therapeutic avenues to attenuate fibrosis by targeting FAPs.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00245.2023