2026-06-14T06:44:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/93322024-10-31T11:59:06Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Iavarone, Francescopaolo
author
Guardiola, Ombretta
author
Scagliola, Alessandra
author
Andolfi, Gennaro
author
Esposito, Federica
author
Serrano, Antonio L
author
Perdiguero, Eusebio
author
Brunelli, Silvia
author
Munoz-Canoves, Pura
author
Minchiotti, Gabriella
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Unión Europea. Comisión Europea
funder
Fundación La Caixa
2020-03-25T14:52:28Z
2020-03-25T14:52:28Z
2020-02-27
EMBO Rep. 2020:e49075
10.15252/embr.201949075
1469-3178
1469-221X
EMBO reports
32107853
http://hdl.handle.net/20.500.12105/9332
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.
eng
Cripto
Duchenne muscular dystrophy
Endothelial-to-Mesenchymal Transition
Macrophage plasticity
Skeletal muscle regeneration
Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle
journal article
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