Shin Kyungshin, Hwang Sang-Gu, Choi Ik Joon, Ko Young-Gyu, Jeong Jaemin, Kwon Heechung
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Science, Seoul, South Korea.
Department of Biotechnology, Korea University, Seoul, South Korea.
Anim Sci J. 2017 Apr;88(4):712-719. doi: 10.1111/asj.12687. Epub 2016 Sep 4.
Satellite cells attached to skeletal muscle fibers play a crucial role in skeletal muscle regeneration. During regeneration, the satellite cells proliferate, migrate to the damaged region, and fuse to each other. Although it is important to determine the cellular mechanisms controlling myoblast behavior, their regulators are not well understood. In this study, we evaluated the roles of Fbxw7 in primary myoblasts and determined its potential as a therapeutic target for muscle disease. We originally found that Fbxw7β, one of the E3 ubiquitin ligase Fbxw7 subtypes, negatively regulates differentiation, proliferation and migration of myoblasts and satellite cells on muscle fiber. However, these phenomena were not observed in myoblasts expressing a dominant-negative, F-box deleted Fbxw7β, mutant. Our results suggest that myoblast differentiation potential and muscle regeneration can be regulated by Fbxw7β.
附着于骨骼肌纤维的卫星细胞在骨骼肌再生中起着关键作用。在再生过程中,卫星细胞增殖,迁移至受损区域,并相互融合。虽然确定控制成肌细胞行为的细胞机制很重要,但其调节因子尚未得到充分了解。在本研究中,我们评估了Fbxw7在原代成肌细胞中的作用,并确定了其作为肌肉疾病治疗靶点的潜力。我们最初发现,E3泛素连接酶Fbxw7亚型之一的Fbxw7β对成肌细胞和肌肉纤维上卫星细胞的分化、增殖和迁移具有负向调节作用。然而,在表达显性负性、F-box缺失的Fbxw7β突变体的成肌细胞中未观察到这些现象。我们的结果表明,Fbxw7β可调节成肌细胞的分化潜能和肌肉再生。