근조직 및 배양 근세포에서의 Dysferlin 발현과 그 의의
Dysferlin Expression in Skeletal muscles of Patients with Myopathy and Cultured Human Myoblast/Myotube
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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
참고문헌 (35)
- "Making sense of the limb-girdle muscular dystrophies", 122, pp.1403~1420 (1999)
- "Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy", 20, pp.31~36 (1998)
- "Distal anterior compartment myopathy: A dysferlin mutation causing a new muscular dystrophy phenotype", 49, pp.130~134 (2001)
- "Dysferlin and muscular dystrophy", 100, pp.142~145 (2000)
- "The earliest pathologic alterations in dysferlinopathy", 56, pp.1472~1481 (2001)
- "The third human FER-1- like protein is highly similar to dysferlin", 68, pp.313~321 (2000)
- "Muscle pathology in dysferlin deficiency", 28, pp.461~470 (2002)
- "Defective membrane repair in dysferlin-deficient muscular dystrophy", 423, pp.168~172 (2003)
- "Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing", 278, pp.50466~50473 (2003)
- "Proteomic investigation of the molecular pathophysiology of dysferlinopathy", 6, pp.379~385 (2006)
- "Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism", 58, pp.190~195 (2005)
- "In vivo and in vitro dysferlin expression in human muscle satellite cells", 63, pp.1104~1113 (2004)
- "Dysferlin and the plasma membrane repair in muscular dystrophy", 14, pp.206~213 (2004)
- "Gene expression profiling in dysferlinopathies using a dedicated muscle microarray", 11, pp.3283~3298 (2002)
- "Proteinand gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients", 211, pp.23~28 (2003)
- "Normal myoblast fusion requires myoferlin", 132, pp.5565~5575 (2005)
- "The sarcolemmal protein dysferlin and caveolin-3 interact in skeletal muscle", 10, pp.1761~1766 (2001)
- "Calcium- sensitive phospholipid binding properties of normal and mutant ferlin C2 domains", 277, pp.22883~22888 (2002)
- "Developmental and tissue-specific regulation of a novel dysferlin isoform", 30, pp.366~374 (2004)
- "Absence of dysferlin alters myogenin expression and delays human muscle differentiation ＂in vitro＂", 281, pp.17092~17098 (2006)
- "Dystrophin protects the sarcolemma from stresses developed during muscle contraction", pp.3710~3714 (1993)
- "Animal models for muscular dystrophy show different patterns of sarcolemmal disruption", 139, pp.375~385 (1997)
- "Dysferlin is a surface membrane-associated protein that is absent in Miyoshi myopathy", 53, pp.1119~1122 (1999)
- "Dysferlin deletion in SJL mice (SJL Dysf) defines a natural model for limb girdle muscular dystrophy 2B", 23, pp.141~142 (1999)
- "Dalakas MC. Regenerating and denervated human muscle fibers and satellite cells express neural cell adhesion molecule recognized by monoclonal antibodies to naturalkiller cells. Ann Neurol 1992", pp.46~52
- "A nematode gene required for sperm vesicle fusion", 110, pp.1073~1081 (1997)
- "Synaptotagmin I functions as a calcium regulator of release probability", 410, pp.41~49 (2001)
- "Loss, restorationand maintenance of plasma membrane integrity", 137, pp.1~4 (1997)
- "Cell surface events during resealing visualized by scanning-electron microscopy", 304, pp.141~146 (2001)
- "Patching plasma membrane disruptions with cytoplasmic membrane", 113, pp.1891~1902 (2000)
- "Gilula NB. Membrane events involved in myoblast fusion. J Cell Biol 1979", pp.411~425
- "Repairing the tears: dysferlin in muscle membrane repair", 9, pp.327~330 (2003)
- "Intracellular accumulation and reduced sarcolemmal expression of dysferlin in limb-girdle muscular dystrophies", 48, pp.902~912 (2000)
- "Variable reduction of caveolin-3 in patients with LGMD2B", MM, 2003, pp.250, 1431~1438
- "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle", 10, pp.1761~1766 (2001)