Abou-Samra Michel, Boursereau Raphaël, Lecompte Sophie, Noel Laurence, Brichard Sonia M
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, Brussels, Belgium.
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, Medical Sector, Catholic University of Louvain, Brussels, Belgium.
Am J Pathol. 2017 Jul;187(7):1577-1585. doi: 10.1016/j.ajpath.2017.02.018. Epub 2017 Apr 29.
Adiponectin (ApN) is a hormone that exhibits anti-inflammatory effects on skeletal muscle exposed to acute and chronic inflammation. We have previously tested the implication of ApN in Duchenne muscular dystrophy (DMD) using mdx mice, a model of DMD, and by generating transgenic mdx mice overexpressing ApN. We showed that ApN can act as a preventive agent and delay disease progression by reducing muscle inflammation/injury and improving force/myogenesis. Herein, we took an opposite approach and crossed mdx mice with ApN knockout mice, to obtain mdx mice with ApN depletion. The aims were to test whether ApN deficiency could worsen the mdx phenotype and whether ApN supplementation can reverse several muscle abnormalities once the disease is settled. mdx-knockout mice exhibited lower muscle force/endurance as well as increased muscle damage when compared to regular mdx mice. Local administration of the ApN gene significantly reduced the expression of several oxidative stress/inflammatory markers and increased the expression of myogenic markers in the skeletal muscle. Finally, the presence of ApN markedly reduced the activity of NF-κB, a key player in muscle inflammation and myogenesis. ApN proves to be a powerful protector of the skeletal muscle capable of reversing the disease progression, thus making it a potential therapeutic agent for DMD.
脂联素（ApN）是一种对暴露于急性和慢性炎症的骨骼肌具有抗炎作用的激素。我们之前使用杜兴氏肌营养不良症（DMD）模型mdx小鼠，并通过生成过表达ApN的转基因mdx小鼠，测试了ApN在DMD中的作用。我们表明，ApN可以作为一种预防剂，通过减轻肌肉炎症/损伤和改善力量/肌生成来延缓疾病进展。在此，我们采取了相反的方法，将mdx小鼠与ApN基因敲除小鼠杂交，以获得ApN缺失的mdx小鼠。目的是测试ApN缺乏是否会使mdx表型恶化，以及ApN补充是否能在疾病稳定后逆转几种肌肉异常。与正常mdx小鼠相比，mdx基因敲除小鼠表现出更低的肌肉力量/耐力以及增加的肌肉损伤。局部施用ApN基因显著降低了几种氧化应激/炎症标志物的表达，并增加了骨骼肌中肌生成标志物的表达。最后，ApN的存在显著降低了NF-κB的活性，NF-κB是肌肉炎症和肌生成中的关键因子。ApN被证明是骨骼肌的有力保护剂，能够逆转疾病进展，因此使其成为DMD的潜在治疗剂。
