The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue eLife Année : 2018

The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration

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Skeletal muscle regeneration depends on satellite cells. After injury these muscle stem cells exit quiescence, proliferate and differentiate to regenerate damaged fibres. We show that this progression is accompanied by metabolic changes leading to increased production of reactive oxygen species (ROS). Using Pitx2/3 single and double mutant mice that provide genetic models of deregulated redox states, we demonstrate that moderate overproduction of ROS results in premature differentiation of satellite cells while high levels lead to their senescence and regenerative failure. Using the ROS scavenger, N-Acetyl-Cysteine (NAC), in primary cultures we show that a physiological increase in ROS is required for satellite cells to exit the cell cycle and initiate differentiation through the redox activation of p38a MAP kinase. Subjecting cultured satellite cells to transient inhibition of P38a MAP kinase in conjunction with NAC treatment leads to their rapid expansion, with striking improvement of their regenerative potential in grafting experiments.
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hal-01908415 , version 1 (30-10-2018)

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Aurore L'Honoré, Pierre-Henri Commère, Elisa Negroni, Giorgia Pallafacchina, Bertrand Friguet, et al.. The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38α MAP kinase and redox regulation of muscle regeneration. eLife, 2018, 7, pp.e32991. ⟨10.7554/eLife.32991⟩. ⟨hal-01908415⟩
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