Yamazaki M, Minota S, Sakurai H, Miyazono K, Yamada A, Kanazawa I, Kawai M
Department of Neurology, Faculty of Medicine, University of Tokyo, Japan.
Am J Pathol. 1994 Feb;144(2):221-6.
Progressive muscular dystrophy is characterized by muscle fiber necrosis, regeneration, and endomysial fibrosis. Although absence of dystrophin has been known as the cause of muscle fiber degeneration, pathogenesis of interstitial fibrosis is still unknown. Transforming growth factor-beta 1 (TGF-beta 1) induces accumulation of extracellular matrix in various diseases, such as liver cirrhosis and interstitial pneumonitis. To investigate its function on the pathogenesis of progressive muscular dystrophy, it was necessary to determine the degree of TGF-beta 1 expression and the site of TGF-beta 1 immunoreactivity. In Duchenne muscular dystrophy and most of Becker muscular dystrophy, high TGF-beta 1 immunoreactivity expressed on muscle fibers and extracellular space. In other myopathies with endomysial fibrosis, however, TGF-beta 1 was seldom observed. We also examined the immunoreactivity of the latent TGF-beta binding protein, which is bound to the TGF-beta precursors. In all Duchenne muscular dystrophy and half of Becker muscular dystrophy cases, high latent TGF-beta 1 binding protein immunoreactivity was seen, but in other myopathies its immunoreactivity was seldom seen on muscle fibers or extracellular space. Therefore TGF-beta 1 may play an important role in synthesis and accumulation of extracellular matrix in progressive muscular dystrophy.
进行性肌营养不良的特征是肌纤维坏死、再生和肌内膜纤维化。虽然已知肌营养不良蛋白的缺失是肌纤维变性的原因，但间质纤维化的发病机制仍不清楚。转化生长因子-β1（TGF-β1）在各种疾病中诱导细胞外基质的积累，如肝硬化和间质性肺炎。为了研究其在进行性肌营养不良发病机制中的作用，有必要确定TGF-β1的表达程度和TGF-β1免疫反应性的部位。在杜兴肌营养不良症和大多数贝克肌营养不良症中，TGF-β1在肌纤维和细胞外空间有高免疫反应性表达。然而，在其他伴有肌内膜纤维化的肌病中，很少观察到TGF-β1。我们还检测了与TGF-β前体结合的潜伏TGF-β结合蛋白的免疫反应性。在所有杜兴肌营养不良症和一半的贝克肌营养不良症病例中，可见高潜伏TGF-β1结合蛋白免疫反应性，但在其他肌病中，在肌纤维或细胞外空间很少见到其免疫反应性。因此，TGF-β1可能在进行性肌营养不良症细胞外基质的合成和积累中起重要作用。
