Cellular Mechanisms of Tissue Fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis
Cellular Mechanisms of Tissue Fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis
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DOI：
10.1152/ajpcell.00173.2013
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发表时间：
2013-08-01
影响因子：
5.5
通讯作者：
Ward, Samuel R.
中科院分区：
文献类型：
--
作者：
Lieber, Richard L.;Ward, Samuel R.
骨骼肌纤维化可能是由多种原因引起的破坏性临床问题，包括肌营养不良症所见的原发骨骼肌组织疾病，也可能是肌肉创伤或脑损伤等事件的继发性疾病。激活的成纤维细胞(肌成纤维细胞)的细胞来源可能包括常驻成纤维细胞、成人肌肉干细胞、炎性细胞或血管周围细胞，这取决于所研究的模型。尽管所有的肌成纤维细胞可能不是单一的来源，但产生纤维化的一个共同机制是通过转化生长因子-β/磷酸化的SMAD3途径。因此，这一途径及其下游靶点为抗纤维化治疗提供了基因座，也为阻断祖细胞向激活的成纤维细胞的转分化提供了方法。骨骼肌胞外胶原网络的结构模型是必需的，以便对胶原含量、形态和基因表达的测量可以与力学性能相关联。用于研究肺、肾和肝脏等组织纤维化的方法需要应用于骨骼肌的研究，以确定预防甚至治愈骨骼肌毁灭性疾病的方法。
Skeletal muscle fibrosis can be a devastating clinical problem that arises from many causes, including primary skeletal muscle tissue diseases, as seen in the muscular dystrophies, or it can be secondary to events that include trauma to muscle or brain injury. The cellular source of activated fibroblasts (myofibroblasts) may include resident fibroblasts, adult muscle stem cells, or inflammatory or perivascular cells, depending on the model studied. Even though it is likely that there is no single source for all myofibroblasts, a common mechanism for the production of fibrosis is via the transforming growth factor-beta/phosphorylated Smad3 pathway. This pathway and its downstream targets thus provide loci for antifibrotic therapies, as do methods for blocking the transdifferentiation of progenitors into activated fibroblasts. A structural model for the extracellular collagen network of skeletal muscle is needed so that measurements of collagen content, morphology, and gene expression can be related to mechanical properties. Approaches used to study fibrosis in tissues, such as lung, kidney, and liver, need to be applied to studies of skeletal muscle to identify ways to prevent or even cure the devastating maladies of skeletal muscle.