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Activation of ß-catenin in mesenchymal progenitors leads to muscle mass loss.
Kajabadi, Nasim; Low, Marcela; Jacques, Erik; Lad, Heta; Tung, Lin Wei; Babaeijandaghi, Farshad; Gamu, Daniel; Zelada, Diego; Wong, Chi Kin; Chang, Chihkai; Yi, Lin; Wosczyna, Michael N; Rando, Thomas A; Henríquez, Juan Pablo; Gibson, William T; Gilbert, Penney M; Rossi, Fabio M V.
Afiliación
  • Kajabadi N; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
  • Low M; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Carrera de Química y Farmacia, Facultad de Medicina y Ciencia, Universidad San Sebastián, General Lagos 1163, 5090000 Valdivia, Chile.
  • Jacques E; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Lad H; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • Tung LW; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
  • Babaeijandaghi F; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
  • Gamu D; BC Children's Hospital Research Institute, 938 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, University of British Columbia, C201, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
  • Zelada D; Neuromuscular Studies Laboratory (NeSt Lab), GDeP, Department of Cell Biology, Universidad de Concepción, Concepción, Chile.
  • Wong CK; BC Children's Hospital Research Institute, 938 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, University of British Columbia, C201, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
  • Chang C; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
  • Yi L; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
  • Wosczyna MN; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Musculoskeletal Research Center, Bioengineering Institute, Department of Orthopedic Surgery, NYU Grossman School of Medicine, New York, NY 10010, USA; Paul F. Glenn Center for the Biol
  • Rando TA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicin
  • Henríquez JP; Neuromuscular Studies Laboratory (NeSt Lab), GDeP, Department of Cell Biology, Universidad de Concepción, Concepción, Chile.
  • Gibson WT; BC Children's Hospital Research Institute, 938 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, University of British Columbia, C201, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
  • Gilbert PM; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
  • Rossi FMV; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: fabio@brc.ubc.ca.
Dev Cell ; 58(6): 489-505.e7, 2023 03 27.
Article en En | MEDLINE | ID: mdl-36898377
Loss of muscle mass is a common manifestation of chronic disease. We find the canonical Wnt pathway to be activated in mesenchymal progenitors (MPs) from cancer-induced cachectic mouse muscle. Next, we induce ß-catenin transcriptional activity in murine MPs. As a result, we observe expansion of MPs in the absence of tissue damage, as well as rapid loss of muscle mass. Because MPs are present throughout the organism, we use spatially restricted CRE activation and show that the induction of tissue-resident MP activation is sufficient to induce muscle atrophy. We further identify increased expression of stromal NOGGIN and ACTIVIN-A as key drivers of atrophic processes in myofibers, and we verify their expression by MPs in cachectic muscle. Finally, we show that blocking ACTIVIN-A rescues the mass loss phenotype triggered by ß-catenin activation in MPs, confirming its key functional role and strengthening the rationale for targeting this pathway in chronic disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Beta Catenina / Vía de Señalización Wnt Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Beta Catenina / Vía de Señalización Wnt Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos