title: Fibrogenic Cell Plasticity Blunts Tissue Regeneration and Aggravates Muscular Dystrophy.
abstract: Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pessina
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Kharraz
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Jardí
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: So-ichiro
authors.initials: S
authors.lastname: Fukada
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Serrano
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Perdiguero
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University (UPF), CIBER on Neurodegenerative Diseases (CIBERNED), Dr. Aiguader, 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys, 23, 08010 Barcelona, Spain. Electronic address: pura.munoz@upf.edu.
authors.forename: Pura
authors.initials: P
authors.lastname: Muñoz-Cánoves
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000066670:Cell Plasticity; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005355:Fibrosis; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C085725:integrin alpha7; D020796:Receptor, Platelet-Derived Growth Factor alpha