Late-Stage Skeletal Muscle Transcriptome in Duchenne Muscular Dystrophy Shows a BMP4-Induced Molecular Signature.

ABSTRACT:

Background

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function variants in the DYSTROPHIN gene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of the TGFβ family of cytokines, like TGFβ1 and BMP4. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation of Smad8 transcription in muscle cells. However, the role of BMP4 in late-stage DMD skeletal muscle is unknown. We hypothesized that BMP4 signalling is a driver of aberrant gene expression in late-stage human DMD skeletal muscle detectable by a transcriptomic signature.

Methods

Transcriptomes from skeletal muscle biopsies of late-stage DMD versus

SUBMITTER: Sothers H 

PROVIDER: S-EPMC12245985 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature