2026-06-14T03:28:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/93322024-10-31T11:59:06Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2020-02-27 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. EMBO Rep. 2020:e49075 10.15252/embr.201949075 1469-3178 1469-221X EMBO reports 32107853 http://hdl.handle.net/20.500.12105/9332 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