Combinatorial activation of the WNT-dependent fibrogenic program by distinct complement subunits in dystrophic muscle

ABSTRACT: Fibrosis is associated with compromised muscle functionality in Duchenne muscular dystrophy (DMD). We report observations with tissues from dystrophic patients and mice supporting a model to explain fibrosis in DMD, which relies on the crosstalk between the complement and the WNT-signaling pathways and the functional interactions of two cellular types. Fibro-adipogenic progenitors and macrophages, which populate the inflamed dystrophic muscles, act as a combinatorial source of WNT-activity by secreting distinct subunits of the C1 complement complex. The resulting aberrant activation of the WNT-signaling in responsive cells, such as fibro-adipogenic progenitors, contributes to fibrosis. Indeed, pharmacological inhibition of the C1r/s subunits in a murine model of DMD mitigated the activatio

SUBMITTER: Prof. Stefano Biressi 

PROVIDER: S-SCDT-10_15252-EMMM_202317405 | biostudies-other |

REPOSITORIES: biostudies-other