miR-378 silencing attenuates dystrophic pathology in the mdx mouse model of Duchenne muscular dystrophy. Mus musculus

The severity of Duchenne muscular dystrophy (DMD), incurable disease caused by the lack of dystrophin, might be modulated by different factors, such as microRNAs (miRNAs). Here we demonstrated that dystrophin-deficient mdx mice lacking additionally miR-378 (dKO animals) exhibited better running capacity than mdx mice. Accordingly, markers of muscle damage and regeneration in serum were markedly decreased in dKO mice followed by diminished inflammation, fibrosis and reduced abundance of regenerative fibers in muscles. Lack of miR-378 normalized also the accelerated differentiation of dystrophin-deficient muscle satellite cells (mSCs). RNA sequencing revealed fibroblast growth factor 1 (Fgf1) as one of the most significantly downregulated genes in the gastrocnemius muscle of mice devoid of miR-378. Treatment with FGF-1 augmented differentiation of dKO mSCs to the level of mdx mSCs, pointing out FGF-1 as one of the mediators of the observed effect. In conclusion, we suggest that targeting miR-378 has the potential to ameliorate DMD pathology.