Resolvin-D2 (RvD2) showed more potent effects than glucocorticoids in reducing inflammation and fibrosis in mice with Duchenne muscular dystrophy (DMD), according to a new study published in Nature Communications.
The authors showed that treatment with RvD2 led to changes in macrophage phenotype, from proinflammatory to anti-inflammatory, and increased the secretion of promyogenic factors. These factors promote myoblast fusion and myotube growth.
In addition, a direct effect of RvD2 on myogenic cells was demonstrated. It promoted the expansion of progenitor cells, as well as myogenic cell differentiation to increase myogenesis.
Hence, mice treated with RvD2 presented with a higher number of myogenic cells than nontreated control mice. They also showed increased muscle fiber size, muscle force, and global physical function.
“Considering that RvD2 and glucocorticoids have similar anti-inflammatory and anti-fibrotic effects on dystrophic muscles, our findings suggest that the superior therapeutic effect of RvD2 is mostly attributable to its capacity to directly target myogenic cells in order to improve myogenesis,” the authors explained.
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They found that RvD2’s anti-inflammatory effect was equivalent after systemic or local delivery, which suggested that its local action in skeletal muscles is not dependent on the administration route.
Resolvins are specialized pro-resolving mediators that originate from omega-3 fatty acids by the action of enzymes like 5-lipoxygenase and 15-lipoxygenase. This group of molecules is known to actively stimulate the resolution of inflammation through multiple mechanisms.
Among others, resolvins block neutrophil infiltration and promote their apoptosis, and stimulate nonphlogistic phagocytosis by macrophages as well as their switch towards an anti-inflammatory phenotype.
The therapeutic potential of resolvins has been demonstrated for several conditions, including asthma, type 2 diabetes, sepsis, and arthritis.
Dort J, Orfi Z, Fabre P, et al. Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy. Nat Commun. 2021;12(1):6264. doi:10.1038/s41467-021-26516-0