Lack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.

缺乏肌营养不良蛋白会导致肌肉退化，而杜氏肌营养不良症 (DMD) 中的慢性炎症和肌肉干细胞再生能力降低会加剧肌肉退化。迄今为止，糖皮质激素仍然是治疗 DMD 的金标准。这些药物能够通过抑制慢性和过度炎症过程来减缓疾病的进展并延长寿命；然而，它们也有许多有害的副作用，阻碍了它们的治疗潜力。在这里，我们研究了 Resolvin-D2 作为一种新的治疗替代方案，它有可能针对导致疾病进展的多个关键特征。我们的体外研究结果表明，Resolvin-D2 促进巨噬细胞向抗炎表型转变，并增加其促生肌因子的分泌。而且，Resolvin-D2 直接靶向肌原细胞并促进它们的分化和肌原祖细胞库的扩张，从而导致肌生成增加。当受体 Gpr18 被药理学拮抗剂 O-1918 敲除、击倒或阻断时，这些作用就会消失。我们使用不同的 DMD 小鼠模型表明，与糖皮质激素相比，Resolvin-D2 同时靶向炎症和肌生成，从而增强肌肉功能。总的来说，这项临床前研究确定了一种新的治疗方法，它比 DMD 的金标准治疗更有效。或被药理学拮抗剂 O-1918 阻断。我们使用不同的 DMD 小鼠模型表明，与糖皮质激素相比，Resolvin-D2 同时靶向炎症和肌生成，从而增强肌肉功能。总的来说，这项临床前研究确定了一种新的治疗方法，它比 DMD 的金标准治疗更有效。或被药理学拮抗剂 O-1918 阻断。我们使用不同的 DMD 小鼠模型表明，与糖皮质激素相比，Resolvin-D2 同时靶向炎症和肌生成，从而增强肌肉功能。总的来说，这项临床前研究确定了一种新的治疗方法，它比 DMD 的金标准治疗更有效。