Abstract
Skeletal muscle is composed of a large and heterogeneous assortment of cell populations that interact with each other to maintain muscle homeostasis and orchestrate regeneration. Although satellite cells (SCs) – which are muscle stem cells – are the protagonists of functional muscle repair following damage, several other cells such as inflammatory, vascular, and mesenchymal cells coordinate muscle regeneration in a finely tuned process. Fibro–adipogenic progenitors (FAPs) are a muscle interstitial mesenchymal cell population, which supports SCs differentiation during tissue regeneration. During the first days following muscle injury FAPs undergo massive expansion, which is followed by their macrophage-mediated clearance and the re-establishment of their steady-state pool. It is during this critical time window that FAPs, together with the other cellular components of the muscle stem cell niche, establish a dynamic network of interactions that culminate in muscle repair. A number of different molecules have been recently identified as important mediators of this cross-talk, and its alteration has been associated with different muscle pathologies. In this review, we will focus on the soluble factors that regulate FAPs activity, highlighting their roles in orchestrating the inter-cellular interactions between FAPs and the other cell populations that participate in muscle regeneration.
Highlights
Skeletal muscle is the most abundant tissue in healthy humans, accounting for 40% of body weight
Recent findings have shown that myogenic cells can produce extra-cellular matrix (ECM) components (Fry et al, 2017b; González et al, 2017; Baghdadi et al, 2018), and a recently identified population of interstitial tenocytes has been implicated in ECM deposition in vivo (Giordani et al, 2019), the main cellular sources of ECM proteins are fibroblasts, myo-fibroblast, and fibro–adipogenic progenitors (FAPs) (Serrano and Muñoz-Cánoves, 2010; Lemos et al, 2015; Contreras et al, 2016; Mueller et al, 2016)
In vitro treatment of Fibro–adipogenic progenitors (FAPs) with IL-15 impaired their capacity to differentiate into adipocytes (Kang et al, 2018), likely through the induction of desert Hedgehog (DHH) signaling, a known repressor of FAPs adipogenesis (Kopinke et al, 2017). These results suggest a positive role for IL-15 in muscle regeneration, the evidence that IL-15 administration, and expression, correlates with increased collagen deposition in vivo after muscle damage (Kang et al, 2018), poses several unresolved issues that warrant further investigation
Summary
Skeletal muscle is the most abundant tissue in healthy humans, accounting for 40% of body weight. Upon muscle injury, FAPs become activated, proliferate and expand, and provide a transient favorable environment to promote SCs-mediated regeneration (Joe et al, 2010; Heredia et al, 2013; Mozzetta et al, 2013).
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