Matrix metalloproteinases are hallmark early biomarkers and therapeutic targets in FSHD.

ABSTRACT: Matrix remodeling by metalloproteinases (MMPs) is essential for maintaining muscle homeostasis; however, their dysregulation can drive degenerative processes. By interrogating biopsy RNA-Seq data, we showed that MMP expression correlated with disease severity in facioscapulohumeral muscular dystrophy (FSHD). In the iDUX4pA FSHD mouse model, MMP levels also progressively increased in response to double homeobox 4-induced (DUX4-induced) muscle degeneration. Single-cell RNA-Seq further identified fibroadipogenic progenitors (FAPs) and macrophages as the primary sources of MMPs, particularly MMP2, MMP14, and MMP19, in dystrophic muscle. Treatment with the pan-MMP inhibitor batimastat alleviated inflammation and fibrosis, improved muscle structure, and decreased the number of FAPs and infiltrat

SUBMITTER: Jung U 

PROVIDER: S-EPMC12643495 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature