Publication Date
11-21-2022
Journal
Nature Communications
DOI
10.1038/s41467-022-34191-y
PMID
36411280
PMCID
PMC9678897
PubMedCentral® Posted Date
11-21-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Mice, Adipogenesis, Follistatin, Macrophages, Mice, Transgenic, Muscles, Mannose Receptor, Monocytes and macrophages, Mesenchymal stem cells
Abstract
Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in impaired muscle stem cell function, enhanced fibrosis, and delayed muscle regeneration. Mechanistically, CD206+ M2-like macrophages inhibit the secretion of FAP-derived follistatin via TGF-β signaling. Here we show that CD206+ M2-like macrophages constitute a microenvironment for FAPs and may regulate the myogenic potential of muscle stem/satellite cells.
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