Department of Orthopaedic Surgery, University of California San Diego, San Diego, California 92093-0863, USA.
Am J Physiol Cell Physiol. 2013 Aug 1;305(3):C241-52. doi: 10.1152/ajpcell.00173.2013. Epub 2013 Jun 12.
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-β/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.
骨骼肌纤维化可能是一个严重的临床问题，它可以由多种原因引起，包括原发性骨骼肌组织疾病，如肌肉营养不良症，也可以继发于包括肌肉创伤或脑损伤在内的事件。激活的成纤维细胞（肌成纤维细胞）的细胞来源可能包括驻留成纤维细胞、成年肌肉干细胞或炎症或血管周围细胞，具体取决于所研究的模型。尽管不太可能存在所有肌成纤维细胞的单一来源，但纤维化的产生可能存在共同的机制，即通过转化生长因子-β/磷酸化 Smad3 途径。因此，该途径及其下游靶标为抗纤维化治疗提供了靶点，阻止祖细胞向激活成纤维细胞的转分化的方法也是如此。需要建立骨骼肌细胞外胶原网络的结构模型，以便将胶原含量、形态和基因表达的测量与机械性能联系起来。需要将用于研究肺、肾和肝等组织纤维化的方法应用于骨骼肌研究，以确定预防甚至治愈骨骼肌破坏性疾病的方法。
