Abe Shinichi, Hirose Daiki, Kado Syotaro, Iwanuma Osamu, Saka Hideki, Yanagisawa Nobuaki, Ide Yoshinobu
Department of Anatomy, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba, Chiba 261-8502, Japan.
Anat Sci Int. 2009 Dec;84(4):305-11. doi: 10.1007/s12565-009-0039-9. Epub 2009 Apr 1.
Satellite cells exist in postnatal muscle tissue and constitute the main source of muscle precursor cells for growth and repair. These cells carry out important roles for skeletal muscle formation postnatally during growth of muscle mass as well as damage-induced regenerative processes. Muscle regeneration supports muscle function in aging and has a role in the functional impairment caused by progressive neuromuscular diseases. Major substances controlling this process are growth factors and extracellular matrix. Myostatin, a member of TGF-beta family, was mainly expressed in muscle tissue. Decorin, a member of the small leucine-rich proteoglycan gene family, is composed of a core protein and a dermatan/chondroitin sulfate chain. Recent studies have shown that decorin enhanced the proliferation and differentiation of myogenic cells by suppressing myostatin activity. Thus, decorin appears to be a new molecule in the myostatin signaling pathway and a promising target for treatment of progressive neuromuscular diseases. Therefore, in this study, we examined the localization of decorin as well as myostatin in a muscular dystrophy model in mdx mice and B10 Scott Snells mice as a control to elucidate the differences between decorin and myostatin messages as well as protein distribution. This study revealed increased expression of decorin protein as well as mRNA at the regenerative stage of mdx mice compared to early stages, while only weak expression of decorin was detected in the control mice. Our study contributes to identifying the relationship between decorin and myostatin as well as the development of a therapeutic strategy for progressive neuromuscular diseases.
卫星细胞存在于出生后的肌肉组织中，是肌肉生长和修复的主要肌肉前体细胞来源。这些细胞在出生后骨骼肌生长以及损伤诱导的再生过程中发挥着重要作用。肌肉再生有助于维持衰老肌肉的功能，并在进行性神经肌肉疾病所致的功能损害中发挥作用。控制这一过程的主要物质是生长因子和细胞外基质。肌肉生长抑制素是转化生长因子-β家族的成员，主要在肌肉组织中表达。核心蛋白聚糖是富含亮氨酸的小分子蛋白聚糖基因家族的成员，由一个核心蛋白和一条硫酸皮肤素/硫酸软骨素链组成。最近的研究表明，核心蛋白聚糖通过抑制肌肉生长抑制素的活性来增强成肌细胞的增殖和分化。因此，核心蛋白聚糖似乎是肌肉生长抑制素信号通路中的一个新分子，也是治疗进行性神经肌肉疾病的一个有前景的靶点。因此，在本研究中，我们检测了核心蛋白聚糖以及肌肉生长抑制素在mdx小鼠肌肉营养不良模型中的定位，并以B10 Scott Snells小鼠作为对照，以阐明核心蛋白聚糖和肌肉生长抑制素在信息以及蛋白质分布上的差异。本研究显示，与早期相比，mdx小鼠再生阶段核心蛋白聚糖蛋白和mRNA的表达增加，而对照小鼠中仅检测到核心蛋白聚糖的微弱表达。我们的研究有助于确定核心蛋白聚糖与肌肉生长抑制素之间的关系，以及为进行性神经肌肉疾病制定治疗策略。
