Skeletal muscle fibrosis develops in response to desmin deletion
Skeletal muscle fibrosis develops in response to desmin deletion
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DOI：
10.1152/ajpcell.00441.2011
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发表时间：
2012-06-01
影响因子：
5.5
通讯作者：
Lieber, Richard L.
中科院分区：
文献类型：
--
作者：
Meyer, Gretchen A.;Lieber, Richard L.
Meyer GA，Lieber RL.骨骼肌纤维化的发展是对结蛋白缺失的反应。Am J Physiol Cell Physiol 302：C1609-C1620，2012.首次发表于2012年3月21日; doi：10.1152/ajpcell.00441.2011。骨骼肌是一种动态的蛋白质复合物，它对内部和外部的提示做出反应，以促进肌肉的适应。在疾病或改变使用的情况下，这些信息可能会被扭曲，导致肌病，如纤维化。在这项工作中，我们描述了一个温和的和渐进的纤维化适应骨骼肌缺乏细胞骨架中间丝蛋白结蛋白。缺乏结蛋白的肌肉变得越来越僵硬，胶原蛋白积累增加，并增加参与细胞外基质周转的基因表达。另外，在结蛋白不存在的情况下，骨骼肌处于增加的炎症和再生状态，如通过增加的中央有核纤维、升高的炎症和再生相关基因表达以及增加的炎性细胞数量所指示的。这些数据表明，在缺乏结蛋白丝网络的细胞骨架支持的肌肉中，细胞损伤增加和纤维化发展之间存在潜在联系。
Meyer GA, Lieber RL. Skeletal muscle fibrosis develops in response to desmin deletion. Am J Physiol Cell Physiol 302: C1609-C1620, 2012. First published March 21, 2012; doi:10.1152/ajpcell.00441.2011.-Skeletal muscle is a dynamic composite of proteins that responds to both internal and external cues to facilitate muscle adaptation. In cases of disease or altered use, these messages can be distorted resulting in myopathic conditions such as fibrosis. In this work, we describe a mild and progressive fibrotic adaptation in skeletal muscle lacking the cytoskeletal intermediate filament protein desmin. Muscles lacking desmin become progressively stiffer, accumulate increased collagen, and increase expression of genes involved in extracellular matrix turnover. Additionally, in the absence of desmin, skeletal muscle is in an increased state of inflammation and regeneration as indicated by increased centrally nucleated fibers, elevated inflammation and regeneration related gene expression, and increased numbers of inflammatory cells. These data suggest a potential link between increased cellular damage and the development of fibrosis in muscles lacking the cytoskeletal support of the desmin filament network.