High resolution three-dimensional reconstruction of fibrotic skeletal muscle extracellular matrix
High resolution three-dimensional reconstruction of fibrotic skeletal muscle extracellular matrix
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DOI：
10.1113/jp273376
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发表时间：
2017-02-01
影响因子：
5.5
通讯作者：
Lieber, Richard L.
中科院分区：
文献类型：
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作者：
Gillies, Allison R.;Chapman, Mark A.;Lieber, Richard L.
骨骼肌细胞外基质（ECM）的结构和组织尚不清楚，但ECM在正常组织稳态和疾病过程中发挥着重要作用。纤维化在许多肌肉疾病中是常见的，并且通常基于ECM胶原蛋白的增加来量化。通过使用多种成像方式和定量体视学，我们描述了野生型和纤维化ECM的结构和组成，我们表明ECM中的胶原蛋白被组织成大束的原纤维或胶原缆线，并且这些缆线的数量（但不是它们的大小）在结蛋白敲除肌肉（纤维化模型）中增加。电缆数量的增加伴随着肌肉僵硬度的增加和胶原蛋白产生细胞数量的增加。ECM细胞和胶原电缆之间的独特的相互作用，也观察到和重建的连续块面扫描电子显微镜。这些结果表明，肌肉ECM比以前报道的更高度组织化。骨骼肌纤维化的治疗策略应考虑ECM的组织，以靶向有助于纤维化肌肉功能的结构和细胞。
Skeletal muscle extracellular matrix (ECM) structure and organization are not well understood, yet the ECM plays an important role in normal tissue homeostasis and disease processes. Fibrosis is common to many muscle diseases and is typically quantified based on an increase in ECM collagen. Through the use of multiple imaging modalities and quantitative stereology, we describe the structure and composition of wild-type and fibrotic ECM, we show that collagen in the ECM is organized into large bundles of fibrils, or collagen cables, and the number of these cables (but not their size) increases in desmin knockout muscle (a fibrosis model). The increase in cable number is accompanied by increased muscle stiffness and an increase in the number of collagen producing cells. Unique interactions between ECM cells and collagen cables were also observed and reconstructed by serial block face scanning electron microscopy. These results demonstrate that the muscle ECM is more highly organized than previously reported. Therapeutic strategies for skeletal muscle fibrosis should consider the organization of the ECM to target the structures and cells contributing to fibrotic muscle function.