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Publication . Article . 2020

Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle

Francescopaolo Iavarone; Ombretta Guardiola; Alessandra Scagliola; Gennaro Andolfi; Federica Esposito; Antonio L. Serrano; Eusebio Perdiguero; +3 Authors
Open Access  
Published: 27 Feb 2020 Journal: EMBO reports, volume 21 (issn: 1469-221X, eissn: 1469-3178, Copyright policy )
Publisher: EMBO
Abstract
Abstract 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 (CriptoMy‐LOF) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, CriptoMy‐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.
The membrane protein Cripto is an extrinsic determinant of macrophage plasticity in skeletal muscle regeneration and disease. Cripto‐dependent modulation of macrophage phenotypes controls endothelial plasticity and contributes to proper muscle repair.
Subjects by Vocabulary

Microsoft Academic Graph classification: Duchenne muscular dystrophy medicine.disease medicine Membrane protein Skeletal muscle medicine.anatomical_structure Biology Cell biology Phenotype Cripto Macrophage SMAD Regeneration (biology)

Subjects

Genetics, Molecular Biology, Biochemistry, cripto; inflammation; macrophages; muscles; regeneration, Cripto, Duchenne muscular dystrophy, Endothelial-to-Mesenchymal Transition, macrophage plasticity, skeletal muscle regeneration, Article, Articles, Cripto, Duchenne muscular dystrophy, Endothelial‐to‐Mesenchymal Transition, macrophage plasticity, skeletal muscle regeneration, Immunology, Molecular Biology of Disease, Signal Transduction, Endothelial-to-Mesenchymal Transition

Funded by
EC| UPGRADE
Project
UPGRADE
Unlocking Precision Gene Therapy
  • Funder: European Commission (EC)
  • Project Code: 825825
  • Funding stream: H2020 | RIA
Validated by funder
,
EC| STEM-AGING
Project
STEM-AGING
Tissue regeneration and aging: the decisive quiescent stem-cell state
  • Funder: European Commission (EC)
  • Project Code: 741966
  • Funding stream: H2020 | ERC | ERC-ADG
Validated by funder