Fig. 7.

Model of the intracellular action of S1P to ameliorate DMD phenotypes. THI treatment leads to increased nuclear S1P levels. Elevated S1P in turn inhibits HDAC2 activity, resulting in increased histone acetylation in the promoter regions of HDAC2 target genes and the upregulation of their expression. The increase in expression of these genes, including miR-1 and miR-29, in turn alleviates fibrosis by decreasing fibrotic gene (Col1α1) expression (target of miR-29), and increases muscle metabolism (metabolic genes are targets of miR-1). Decreased fibrosis and increased muscle metabolism are both beneficial effects on dystrophic muscle.