Goldspink G, Fernandes K, Williams P E, Wells D J
Department of Anatomy and Developmental Biology, Royal Free Hospital School of Medicine, University of London, UK.
Neuromuscul Disord. 1994 May;4(3):183-91. doi: 10.1016/0960-8966(94)90019-1.
It has been shown that there is a marked accumulation of collagen (notably type III) in the muscles of Duchenne muscular dystrophy patients. Although not as marked, there is also an accumulation of collagen in normal skeletal muscle with age. To attempt to determine whether dystrophy-related and/or age-related collagen accumulation are the result of increased collagen gene expression, sections from muscles of mdx and control mice at different ages were subjected to in situ hybridization with cRNA probes for procollagen I and III to estimate changes in specific mRNA levels. Greater amounts of collagen I and III mRNA were noted in skeletal muscles and the diaphragm of the mdx mice than in the same muscles of age matched controls. The over-expression of these collagen genes was particularly noticeable in the mdx diaphragm and may possibly be explained by the greater activity of this muscle as compared to the limb muscles of these dystrophic mice. There was, however, an age-related decline of collagen expression in both normal and dystrophic muscle and this strongly suggests that the increased fibrosis of skeletal muscle with age is not the result of increased collagen gene expression but is most likely due to an impairment of degradation. In contrast, the excess accumulation of collagen in dystrophic muscle compared to normal muscle is related to increased gene expression, probably triggered by an injured tissue response induced by muscle fibre damage due to the lack of dystrophin.
研究表明，杜兴氏肌营养不良症患者的肌肉中存在明显的胶原蛋白（尤其是III型）积累。正常骨骼肌中随着年龄增长也会有胶原蛋白积累，不过没有那么明显。为了确定与营养不良相关和/或与年龄相关的胶原蛋白积累是否是胶原蛋白基因表达增加的结果，对不同年龄的mdx小鼠和对照小鼠的肌肉切片进行了原位杂交，使用前胶原I和III的cRNA探针来估计特定mRNA水平的变化。mdx小鼠的骨骼肌和膈肌中胶原蛋白I和III的mRNA含量高于年龄匹配的对照小鼠的相同肌肉。这些胶原蛋白基因的过度表达在mdx膈肌中尤为明显，这可能是因为与这些营养不良小鼠的肢体肌肉相比，这块肌肉的活动更多。然而，正常和营养不良肌肉中胶原蛋白表达都存在与年龄相关的下降，这强烈表明骨骼肌随年龄增长而增加的纤维化不是胶原蛋白基因表达增加的结果，很可能是由于降解受损。相比之下，与正常肌肉相比，营养不良肌肉中胶原蛋白的过量积累与基因表达增加有关，这可能是由由于缺乏抗肌萎缩蛋白导致的肌纤维损伤引发的组织损伤反应所触发的。
