| First Author | Florio F | Year | 2023 |
| Journal | EMBO Mol Med | Volume | 15 |
| Issue | 12 | Pages | e17405 |
| PubMed ID | 37927228 | Mgi Jnum | J:343303 |
| Mgi Id | MGI:7564704 | Doi | 10.15252/emmm.202317405 |
| Citation | Florio F, et al. (2023) Combinatorial activation of the WNT-dependent fibrogenic program by distinct complement subunits in dystrophic muscle. EMBO Mol Med 15(12):e17405 |
| abstractText | 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 activation of the WNT signaling pathway, reduced the fibrogenic characteristics of the fibro-adipogenic progenitors, and ameliorated the dystrophic phenotype. These studies shed new light on the molecular and cellular mechanisms responsible for fibrosis in muscular dystrophy and open to new therapeutic strategies. |
