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Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle
Author(s) -
Iavarone Francescopaolo,
Guardiola Ombretta,
Scagliola Alessandra,
Andolfi Gennaro,
Esposito Federica,
Serrano Antonio,
Perdiguero Eusebio,
Brunelli Silvia,
MuñozCánoves Pura,
Minchiotti Gabriella
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949075
Subject(s) - humanities , library science , biology , medicine , art , computer science
Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (Cripto My‐LOF ) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, Cripto My‐LOF macrophages infiltrate the muscle, but fail to properly expand as anti‐inflammatory CD206 + macrophages, which is due, at least in part, to aberrant activation of TGFβ/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial‐to‐Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle‐infiltrating macrophages, Cripto is required to promote the expansion of the CD206 + anti‐inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.