Lluri Gentian, Jaworski Diane M
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Avenue, HSRF 418, Burlington, Vermont 05405, USA.
Muscle Nerve. 2005 Oct;32(4):492-9. doi: 10.1002/mus.20383.
Matrix metalloproteinases (MMPs) are zinc-dependent proteases capable of degrading extracellular matrix components. The activity of these proteases is tightly regulated through the actions of the tissue inhibitors of metalloproteinases (TIMPs). Although the regulation of MMPs and TIMPs during physiological and pathological remodeling has been investigated in a number of systems, almost nothing is known about their role in skeletal muscle differentiation. To investigate the role of MMP-mediated proteolysis during myogenesis, the regulation of TIMP-2, MT1-MMP, and MMP-2 expression was investigated during differentiation of the mouse myoblastic C2C12 cell line. We show that this trio is upregulated coincident with myogenesis. The more diffuse spatial distribution of TIMP-2 relative to MT1-MMP and MMP-2 suggests that TIMP-2 may exert MMP-independent functions during myogenesis. Elucidating the regulation of these molecules during muscle differentiation in vitro may lead to a better understanding of their role in pathological processes in muscle tissue in vivo.
基质金属蛋白酶（MMPs）是一类依赖锌的蛋白酶，能够降解细胞外基质成分。这些蛋白酶的活性通过金属蛋白酶组织抑制剂（TIMPs）的作用受到严格调控。尽管在许多系统中已经研究了生理和病理重塑过程中MMPs和TIMPs的调控，但它们在骨骼肌分化中的作用几乎一无所知。为了研究MMP介导的蛋白水解在肌生成过程中的作用，我们在小鼠成肌细胞C2C12细胞系分化过程中研究了TIMP-2、MT1-MMP和MMP-2表达的调控。我们发现这三者在肌生成过程中同时上调。相对于MT1-MMP和MMP-2，TIMP-2更弥散的空间分布表明TIMP-2可能在肌生成过程中发挥不依赖MMP的功能。阐明这些分子在体外肌肉分化过程中的调控机制，可能有助于更好地理解它们在体内肌肉组织病理过程中的作用。
