AGE-RELATED CHANCES IN COLLAGEN GENE-EXPRESSION IN THE MUSCLES OF MDX DYSTROPHIC AND NORMAL MICE

AGE-RELATED CHANCES IN COLLAGEN GENE-EXPRESSION IN THE MUSCLES OF MDX DYSTROPHIC AND NORMAL MICE
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DOI:
10.1016/0960-8966(94)90019-1
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发表时间:
1994-05-01
影响因子:
2.8
通讯作者:
WELLS, DJ
WELLS, DJ
中科院分区:
医学4区
文献类型:
--
作者:
GOLDSPINK, G;FERNANDES, K;WELLS, DJ

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研究表明,杜氏肌营养不良患者的肌肉中有明显的胶原蛋白积累(尤其是III型)。虽然不那么明显,但随着年龄的增长,正常骨骼肌中的胶原蛋白也会积累。为了确定与营养不良相关和/或与年龄相关的胶原积累是否是胶原基因表达增加的结果,我们使用cRNA探针原位氢化mdx和对照小鼠不同年龄的肌肉切片,以检测前胶原I和III的特异性mRNA水平的变化。mdx小鼠的骨骼肌和膈肌中胶原I和III mRNA的含量高于年龄匹配的对照组。这些胶原蛋白基因的过度表达在mdx横膈膜中特别明显,这可能是由于与这些营养不良小鼠的肢体肌肉相比,该肌肉的活动更大。然而,在正常肌肉和营养不良肌肉中,胶原蛋白表达都与年龄相关,这强烈表明骨骼肌纤维化随着年龄的增长不是胶原蛋白基因表达增加的结果,而很可能是由于降解受损。相反,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的增加有关,这可能是由于缺乏营养不良蛋白引起的肌纤维损伤引起的组织损伤反应引起的。
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 hydridization 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.