Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy
Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy
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DOI：
10.1016/j.ajpath.2017.04.011
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发表时间：
2017-08-01
影响因子：
6
通讯作者：
Diaz-Manera, Jordi
中科院分区：
文献类型：
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作者：
Pinol-Jurado, Patricia;Gallardo, Eduard;Diaz-Manera, Jordi
杜氏肌营养不良症（DMD）的特征在于肌纤维的进行性损失，并且它们被纤维化和脂肪组织替代。许多因素促成了这一过程，但与肌肉再生和退化相关的分子途径尚不完全清楚。血小板衍生生长因子（PDGF）-BB属于调节间充质细胞增殖、迁移和分化的生长因子家族。PDGF-BB在人类肌肉再生中的作用尚未研究。我们分析了PDGF-BB在对照组和DMD患者肌肉活检样本中的表达。我们进行了体外实验以了解PDGF-BB对参与肌营养不良症病理生理学的成肌细胞的作用，并通过用重复i.m.注射PDGF-BB。我们观察到DMD患者肌肉活检样本中再生和坏死的肌纤维表达PDGF-BB。在体外，PDGF-BB吸引成肌细胞并激活其增殖。对用PDGF-BB处理的动物的肌肉的分析显示，与溶剂处理的小鼠相比，卫星细胞的数量增加，再生纤维的数量增加，炎性浸润减少。基于我们的研究结果，PDGF-BB可能通过激活卫星细胞增殖和迁移来增强肌肉再生，从而在肌营养不良症中发挥保护作用。
Duchenne muscular dystrophy (DMD) is characterized by a progressive Loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed in vitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results in vivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. In vitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration.