Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.
Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.
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DOI：
10.1371/journal.pone.0040686
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lieber RL
中科院分区：
文献类型：
--
作者：
Smith LR;Chambers HG;Subramaniam S;Lieber RL
脑性瘫痪（CP）是一种上运动神经元疾病，导致一系列运动障碍。继发于神经系统病变，CP患者的肌肉通常痉挛并形成使人衰弱的挛缩，限制了运动范围和关节功能。由于没有遗传成分，CP中骨骼肌的病理学是对异常复杂神经输入的反应，其方式尚未完全了解。本研究的目的是获得进一步了解骨骼肌反应CP使用转录谱相关的功能措施，广泛调查肌肉适应导致机械缺陷。从接受手术的CP患者（n = 10）和典型发育患者（n =10）队列的股薄肌和半腱肌获得活检。 获得活检以确定挛缩的独特表达谱，并进行被动机械测试以确定先前发表的工作中的刚度值。Affytek HG-U133 A 2.0芯片（n = 40）生成表达数据，使用定量实时PCR对所选转录物进行验证。 芯片基于其表达进行聚类，并且来自CP患者的芯片单独聚类。基于三种汇总算法的重叠保守地确定显著基因（n = 1，398）。 显著改变的基因被分析为在基因本体和肌肉特异性网络之间的过度表示。大多数改变的转录本与CP中细胞外基质表达的增加以及代谢和遍在蛋白连接酶活性的降低有关。细胞外基质产物的增加与机械措施相关，表明残疾的重要性。这些数据为进一步研究和开发新的治疗方法奠定了基础。
Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits. Biospsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10) and typically developing patients (n = 10) undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n = 1,398). Significantly altered genes were analyzed for over-representation among gene ontologies and muscle specific networks. The majority of altered transcripts were related to increased extracellular matrix expression in CP and a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and development of novel therapies.
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DOI：
10.1111/j.1469-8749.2003.tb00954.x
发表时间：
2003-08-01
影响因子：
3.8
作者：
Elder, GCB;Kirk, J;Leahey, L
通讯作者：
Leahey, L
影响因子：
3.4
作者：
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通讯作者：
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DOI：
10.1097/00006205-199602000-00004
发表时间：
1996-02-01
期刊：
The Nurse practitioner
影响因子：
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作者：
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通讯作者：
Yucha, C B
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Blau HM
影响因子：
13
作者：
Husmann, Irene;Soulet, Laurent;Barritault, Denis
通讯作者：
Barritault, Denis