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Muscle cachexia is regulated by a p53--PW1/Peg3-dependent pathway.
- Source :
-
Genes & Development . 12/15/2006, Vol. 20 Issue 24, p8-8. 1p. - Publication Year :
- 2006
-
Abstract
- Muscle wasting (cachexia) is an incurable complication associated with chronic infection and cancers that leads to an overall poor prognosis for recovery. Tumor necrosis factor-α (TNFα) is a key inflammatory cytokine associated with cachexia. TNFα inhibits myogenic differentiation and skeletal muscle regeneration through downstream effectors of the p53 cell death pathway including PW1/Peg3, bax, and caspases. We report that p53 is required for the TNFα-mediated inhibition of myogenesis in vitro and contributes to muscle wasting in response to tumor load in vivo. We further demonstrate that PW1 and p53 participate in a positive feedback regulatory loop in vitro. Consistent with this observation, we find that the number of PW1-expressing stem cells in skeletal muscle declines significantly in p53 nullizygous mice. Furthermore, gene transfer of a dominant-negative form of PW1 into muscle tissue in vivo blocks myofiber atrophy in response to tumor load. Taken together, these results show a novel role for p53 in mediating muscle stem cell behavior and muscle atrophy, and point to new targets for the therapeutic treatment of muscle wasting. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CACHEXIA
*MUSCLES
*INFECTION
*CANCER
*TUMOR necrosis factors
*MYOGENESIS
*STEM cells
Subjects
Details
- Language :
- English
- ISSN :
- 08909369
- Volume :
- 20
- Issue :
- 24
- Database :
- Academic Search Index
- Journal :
- Genes & Development
- Publication Type :
- Academic Journal
- Accession number :
- 23724253
- Full Text :
- https://doi.org/10.1101/gad.412606