Quirico-Santos T, Ribeiro M M, Savino W
Department of Pathology, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
J Neuroimmunol. 1995 Jun;59(1-2):9-18. doi: 10.1016/0165-5728(95)00010-y.
The present work describes the expression of extracellular proteins in the thymus and skeletal muscle of the X-linked dystrophic MDX mouse which corresponds to an experimental model for the human disease Duchenne muscular dystrophy. MDX dystrophic mice showed marked alterations in the thymic cytoarchitecture including cortical atrophy that was paralleled by denser epithelial cell network with intense immunolabelling for cytokeratins pair 8/18 and increased vascularization assessed with monoclonal antibody anti-desmin. Consistent augmentation of intrathymic extracellular matrix components (ECM) was observed especially at weaning and by the onset of disease. Interestingly, the amount of ECM elements in the gastrocnemius muscle of MDX wild-type dystrophic mice also showed a prominent difference as compared to age-matched non-dystrophic BALB/cAn animals. A marked but uneven overdeposition of reticulin and collagen fibres (type I, type IV), laminin and fibronectin were often present in the skeletal muscle of dystrophic mice, mostly around lesioned fibres. Alterations in both organs positively correlated with the degree of dystrophy thus suggesting that similar stimuli may be enhancing ECM production in both thymus and skeletal muscle. Although the thymus gland might not be directly involved in the development of the murine X-linked muscular dystrophy, it should be considered as a further target in this disease.
本研究描述了X连锁营养不良型MDX小鼠胸腺和骨骼肌中细胞外蛋白的表达情况，该小鼠对应于人类杜兴氏肌营养不良症的实验模型。MDX营养不良小鼠胸腺细胞结构出现明显改变，包括皮质萎缩，同时伴有更密集的上皮细胞网络，细胞角蛋白8/18免疫标记强烈，用抗结蛋白单克隆抗体评估显示血管生成增加。尤其在断奶时和疾病发作时，观察到胸腺内细胞外基质成分（ECM）持续增加。有趣的是，与年龄匹配的非营养不良BALB/cAn动物相比，MDX野生型营养不良小鼠腓肠肌中ECM成分的量也存在显著差异。在营养不良小鼠的骨骼肌中，经常出现明显但不均匀的网状纤维和胶原纤维（I型、IV型）、层粘连蛋白和纤连蛋白过度沉积，主要围绕受损纤维。两个器官的改变与营养不良程度呈正相关，因此表明类似的刺激可能会增强胸腺和骨骼肌中ECM的产生。虽然胸腺可能不直接参与小鼠X连锁肌营养不良的发展，但在这种疾病中它应被视为另一个靶点。
