Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression
Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression
复制标题
DOI：
10.1096/fj.06-7285com
复制
发表时间：
2007-04-01
期刊：
影响因子：
4.8
通讯作者：
Ricci, Enzo
中科院分区：
文献类型：
--
作者：
Pescatori, Mario;Broccolini, Aldobrando;Ricci, Enzo
Duchenne型肌营养不良症（DMD）患者骨骼肌的全基因组基因表达谱已被用于描述5岁以上DMD儿童的肌肉组织变化。通过研究19例年龄小于2岁的患者的表达谱，我们以高分辨率描述了DMD肌肉在疾病的初始或“症状前”阶段的基因表达特征。我们发现，在疾病的前2年，DMD肌肉已经表达了一种独特的基因表达模式，与正常的、年龄匹配的肌肉表达的基因表达模式截然不同。这种“营养不良”分子特征的特征在于参与炎症反应、细胞外基质（ECM）重塑和肌肉再生的基因的协调诱导，以及参与能量代谢的那些基因的转录减少。尽管经历的肌肉功能障碍程度较低，但我们的年轻患者显示出大多数基因的异常表达，这些基因在疾病的更晚期阶段被报道为差异表达。通过分析我们的患者作为一个时间序列，我们提供的证据表明，一些基因，包括成员的三个途径参与形态发生信号Wnt，Notch和BMP-进行性诱导或抑制在DMD的自然历史。
Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.