Selective ablation of Nfix in macrophages attenuates muscular dystrophy by inhibiting fibro-adipogenic progenitor-dependent fibrosis.

ABSTRACT: Muscular dystrophies are genetic diseases characterized by chronic inflammation and fibrosis. Macrophages are immune cells that sustain muscle regeneration upon acute injury but seem deleterious in the context of chronic muscle injury such as in muscular dystrophies. Here, we observed that the number of macrophages expressing the transcription factor Nfix increases in two distinct mouse models of muscular dystrophies. We showed that the deletion of Nfix in macrophages in dystrophic mice delays the establishment of fibrosis and muscle wasting, and increases grasp force. Macrophages lacking Nfix expressed more TNFα and less TGFβ1, thus promoting apoptosis of fibro-adipogenic progenitors. Moreover, pharmacological treatment of dystrophic mice with a ROCK inhibitor accelerated fibrosis through

SUBMITTER: Saclier M 

PROVIDER: S-EPMC9322546 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature