PTBP1 inhibition reprograms myogenesis to rescue impaired muscle regeneration in mdx mice through correcting E2A splicing - PubMed
3 hours ago
- #Duchenne muscular dystrophy
- #PTBP1
- #muscle regeneration
- PTBP1 inhibition reprograms myogenesis to rescue impaired muscle regeneration in mdx mice by correcting E2A splicing.
- Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, leading to impaired muscle regeneration.
- Alternative splicing of transcription factor E2-alpha (E12 and E47) plays a key role in myogenic progression.
- E47 promotes myoblast proliferation, while E12 drives myogenic commitment during differentiation.
- Polypyrimidine tract binding protein 1 (PTBP1) regulates E2-alpha splicing; its levels decline during normal myoblast differentiation.
- In DMD patients and mdx mice, PTBP1 remains elevated, disrupting E47/E12 ratios and impairing muscle regeneration.
- PTBP1 knockdown restores myoblast differentiation, enhances muscle repair, and improves muscle function in mdx mice.
- Dergrasyn, a deubiquitinase inhibitor, induces PTBP1 degradation, restoring myogenic differentiation and ameliorating dystrophic pathology.
- PTBP1 is identified as a potential therapeutic target for DMD, with E2-alpha splicing modulation as a promising strategy.