Reduced RECK levels accelerate skeletal muscle differentiation, improve muscle regeneration, and decrease fibrosis

dc.contributor.authorGutierrez, Jaime
dc.contributor.authorGonzalez, David
dc.contributor.authorEscalona-Rivano, Rodrigo
dc.contributor.authorTakahashi, Chiaki
dc.contributor.authorBrandan, Enrique
dc.date.accessioned2025-01-20T22:21:01Z
dc.date.available2025-01-20T22:21:01Z
dc.date.issued2021
dc.description.abstractThe muscle regeneration process requires a properly assembled extracellular matrix (ECM). Its homeostasis depends on the activity of different matrix-metalloproteinases (MMPs). The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) is a membrane-anchored protein that negatively regulates the activity of different MMPs. However, the role of RECK in the process of skeletal muscle differentiation, regeneration, and fibrosis has not been elucidated. Here, we show that during skeletal muscle differentiation of C2C12 myoblasts and in satellite cells on isolated muscle fibers, RECK is transiently up regulated. C2C12 myoblasts with reduced RECK levels are more prone to enter the differentiation program, showing an accelerated differentiation process. Notch-1 signaling was reduced, while p38 and AKT signaling were augmented in myoblasts with decreased RECK levels. Overexpression of RECK restores the normal differentiation process but diminished the ability to form myotubes. Transient up-regulation of RECK occurs during skeletal muscle regeneration, which was accelerated in RECK-deficient mice (Reck +/-). RECK, MMPs and ECM proteins augmented in chronically damaged WT muscle, a model of muscle fibrosis. In this model, RECK +/- mice showed diminished fibrosis compared to WT. These results strongly suggest that RECK is acting as a potential myogenic repressor during muscle formation and regeneration, emerging as a new player in these processes, and as a potential target to treat individuals with the muscle-wasting disease.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.202001646RR
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.202001646RR
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94639
dc.identifier.wosidWOS:000645260100028
dc.issue.numero5
dc.language.isoen
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectMMP
dc.subjectmuscle fibrosis
dc.subjectRECK
dc.subjectregeneration
dc.subjectskeletal muscle differentiation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleReduced RECK levels accelerate skeletal muscle differentiation, improve muscle regeneration, and decrease fibrosis
dc.typeartículo
dc.volumen35
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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