Role of TGF-β/SMAD/YAP/TAZ signaling in skeletal muscle fibrosis
Felipe S. Gallardo, Meilyn Cruz-Soca, Alexia Bock-Pereda, Jennifer Faundez-Contreras, Cristian Gutiérrez‐Rojas, Alessandro Gandin, Veronica Torresan, Juan Carlos Casar, Andrea Ravasio, Enrique Brandan
Abstract
The understanding of the nuclear factors governing the differentiation of muscular fibro/adipogenic progenitors (FAPs) into myofibroblasts is in its infancy. Here, we comprehensively elucidate the status, regulation, and role of the mechanotransducers Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in the muscular fibrotic process. Our findings reveal that inhibiting cellular mechanotransduction limits FAP differentiation and the extent of muscular fibrosis exerted by transforming growth factor type β (TGF-β). This research shed new lights on the molecular mechanisms dictating the cell fate of FAPs and the muscular fibrosis.