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Journal Articles Journal of Cell Science Year : 2021

Interplay between myofibers and pro-inflammatory macrophages controls muscle damage in mdx mice

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Ha My Ly
  • Function : Author
Rémi Mounier
Bénédicte Chazaud
Gaëtan Juban
  • Function : Author
  • PersonId : 1097221
Ha My Ly
  • Function : Author

Abstract

ABSTRACT Duchenne muscular dystrophy is a genetic muscle disease characterized by chronic inflammation and fibrosis mediated by a pro-fibrotic macrophage population expressing pro-inflammatory markers. Our aim was to characterize cellular events leading to the alteration of macrophage properties and to modulate macrophage inflammatory status using the gaseous mediator hydrogen sulfide (H2S). Using co-culture experiments, we first showed that myofibers derived from mdx mice strongly skewed the polarization of resting macrophages towards a pro-inflammatory phenotype. Treatment of mdx mice with NaHS, an H2S donor, reduced the number of pro-inflammatory macrophages in skeletal muscle, which was associated with a decreased number of nuclei per fiber, as well as reduced myofiber branching and fibrosis. Finally, we established the metabolic sensor AMP-activated protein kinase (AMPK) as a critical NaHS target in muscle macrophages. These results identify an interplay between myofibers and macrophages where dystrophic myofibers contribute to the maintenance of a highly inflammatory environment sustaining a pro-inflammatory macrophage status, which in turn favors myofiber damage, myofiber branching and establishment of fibrosis. Our results also highlight the use of H2S donors as a potential therapeutic strategy to improve the dystrophic muscle phenotype by dampening chronic inflammation. This article has an associated First Person interview with the first author of the paper.
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Dates and versions

inserm-03404658 , version 1 (26-10-2021)

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Marielle Saclier, Sabrina Ben Larbi, Ha My Ly, Eugénie Moulin, Rémi Mounier, et al.. Interplay between myofibers and pro-inflammatory macrophages controls muscle damage in mdx mice. Journal of Cell Science, 2021, 134 (18), pp.jcs258429. ⟨10.1242/jcs.258429⟩. ⟨inserm-03404658⟩
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