Pharmacological inhibition of HDAC6 downregulates TGF-β via Smad2/3 acetylation and improves dystrophin-deficient muscles.
Osseni, A.; Ravel-Chapuis, A.; Scionti, I.; Gangloff, Y.-G.; Moncollin, V.; Mounier, R.; Leblanc, P.; Jasmin, B. J.; Schaeffer, L.
Show abstract
Abstract / SummaryThe absence of dystrophin in Duchenne muscular dystrophy (DMD) disrupts the dystrophin dystroglycan glycoprotein complex (DGC) resulting in fibers fragility and atrophy, associated with fibrosis and microtubules and neuromuscular junction (NMJ) disorganization. The specific non-conventional cytoplasmic histone deacetylase 6 (HDAC6) was previously shown to regulate acetylcholine receptor distribution and muscle atrophy. Here we show that administration of the HDAC6 specific inhibitor tubastatin A to the DMD mouse model mdx improves muscle strength, restores microtubules, NMJ and DGC organization, and reduces muscle atrophy and fibrosis. These effects involve the known action of HDAC6 on microtubules acetylation and muscle atrophy but also involve a yet undiscovered action of HDAC6 on transforming growth factor beta (TGF-{beta}) signaling. Conversely, to inhibitors of nuclear HDACs that regulate TGF-{beta} signaling via the activation of Follistatin expression, HDAC6 inhibition acts downstream of TGF-{beta} ligands and receptors by increasing Smad2/3 acetylation in the cytoplasm which in turn inhibits its phosphorylation and transcriptional activity.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration 96%
- The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms 96%
- Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance 95%
Similar papers in this journal
- Tumor-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism 94%
- Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy. 94%
- Cholesterol metabolism is a potential therapeutic target in Duchenne Muscular Dystrophy 94%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis 97%
- Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation 95%
- MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.