근조직 및 배양 근세포에서의 Dysferlin 발현과 그 의의

Abstract

Background: Dysferlin is a 230 kDa protein of the sarcolemma. This encoding gene is mutated in patients with dysferlinopathy (limb-girdle muscular dystrophy 2B and Miyoshi myopathy), which is characterized byan active muscle degeneration and regeneration process. Dysferlin is known to play an essential role in muscle signaling and muscle fiber repair. We studied the gene to define its functional role in muscle repair and differentiation in human skeletal muscle of the patients with myopathies and cultured human myoblast. Methods: An immunohistochemical analysis of dysferlin and N-CAM in biopsied muscle tissue obtained from eleven patients with myopathies [six patients with Duchenne muscular dystrophy (DMD), two patients with dermatomyositis (DM), two patients with polymyositis (PM), and one patient with dysferlinopathy (MM)] and eight normal controls. Cultured human myoblast obtained from normal muscle tissue was also analyzed by the expression of dysferlin through immunocytochemical staining and western blot. Results: The immunoreactivity of dysferlin was strongly expressed in regenerative muscle fibers of myopathies except dysferlinpathy, which was co-localization with N-CAM by double immunohistochemistry. By western blot analysis, the expression level of dysferlin was variable in myopathies compared to normal controls, but no expression in dyferlinopathy. The expression of dysferlin in myotubes was significantly increased compared to that in myoblast by immunostaining and western blot analysis. Conclusions: These results indicated that the expression of dysferlin increased in regenerative and degenerative muscle fibers and also increased in myoblast differentiation. Our study supports that dysferlin not only has a role in skeletal muscle development but also in regeneration/repair process. KeyWords:Dysferlin, Myopathy, Myoblast, Degeneration, Regeneration, Differentiation