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Lookup NU author(s): Professor Laura GreavesORCiD, Professor Robert Taylor
The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild upregulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.
Author(s): Di Foggia V, Zhang XY, Licastro D, Gerli MFM, Phadke R, Muntoni F, Mourikis P, Tajbakhsh S, Ellis M, Greaves LC, Taylor RW, Cossu G, Robson LG, Marino S
Publication type: Article
Publication status: Published
Journal: Journal of Experimental Medicine
Year: 2014
Volume: 211
Issue: 13
Pages: 2617-2633
Print publication date: 15/12/2014
Online publication date: 01/12/2014
Acceptance date: 10/11/2014
Date deposited: 05/08/2015
ISSN (print): 0022-1007
ISSN (electronic): 1540-9538
Publisher: Rockefeller University Press
URL: http://dx.doi.org/10.1084/jem.20140317
DOI: 10.1084/jem.20140317
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