Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model

This study shows for the first time that either CBP overexpression or pan-HDAC inhibition are able to prevent, or at least delay, early stages of muscle damage in zebrafish dystrophic muscles. This observation adds up to the recognised positive effect of HDAC inhibitors on muscle regeneration upon damage 1. Other authors observed that treating mouse dystrophic muscles (mdx) with deacetylase inhibitors was able to confer resistance to contraction-coupled degeneration 14. However, this was suggested to be mediated by follistatin through satellite cell number increase. We show that damage protection occurs independently from regeneration. Follistatin upregulation is not involved in protecting early zebrafish muscle from damage, supporting the idea that the two rescuing mechanisms triggered by HDAC inhibition are independent. That the effect of TSA on follistatin expression differs according to the cellular context is not surprising. What we report here is a muscle-cell autonomous effect of TSA preventing degeneration, and in this context we observed a downregulation of follistatin. Other authors focused on a later effect on regeneration of already damaged muscles, mediated by satellite cells stimulation 1,5,6. In this context, follistatin was found to be upregulated. However, it was shown that TSA promotes follistatin upregulation in the fibroadipogenic progenitors rather than in the muscle satellite cells, and the stimulating effect is paracrine 7,15. Interestingly, overexpress...
Source: PLOS Currents Muscular Dystrophy - Category: Neurology Authors: Source Type: research