Ghajar Cyrus M, George Steven C, Putnam Andrew J
Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Crit Rev Eukaryot Gene Expr. 2008;18(3):251-78. doi: 10.1615/critreveukargeneexpr.v18.i3.30.
Matrix metalloproteinases (MMPs) play crucial roles in a variety of normal (e.g., blood vessel formation, bone development) and pathophysiological (e.g., wound healing, cancer) processes. This is not only due to their ability to degrade the surrounding extracellular matrix (ECM), but also because MMPs function to reveal cryptic matrix binding sites, release matrix-bound growth factors inherent to these processes, and activate a variety of cell surface molecules. The process of blood vessel formation, in particular, is regulated by what is widely classified as the angiogenic switch: a mixture of both pro- and antiangiogenic factors that function to counteract each other unless the stimuli from one side exceeds the other to disrupt the quiescent state. Although it was initially thought that MMPs were strictly proangiogenic, new functions for this proteolytic family, such as mediating vascular regression and generating matrix fragments with antiangiogenic capacities, have been discovered in the last decade. These findings cast MMPs as multifaceted pro- and antiangiogenic effectors. The purpose of this review is to introduce the reader to the general structure and characterization of the MMP family and to discuss the temporal and spatial regulation of their gene expression and enzymatic activity in the following crucial steps associated with angiogenesis: degradation of the vascular basement membrane, proliferation and invasion of endothelial cells within the subjacent ECM, organization into immature tubules, maturation of these nascent vessels, and the pruning and regression of the vascular network.
基质金属蛋白酶（MMPs）在多种正常（如血管形成、骨骼发育）和病理生理（如伤口愈合、癌症）过程中发挥着关键作用。这不仅是因为它们具有降解周围细胞外基质（ECM）的能力，还因为MMPs能够揭示隐藏的基质结合位点，释放这些过程中固有的基质结合生长因子，并激活多种细胞表面分子。特别是血管形成过程，受到广泛分类为血管生成开关的调节：这是一种促血管生成因子和抗血管生成因子的混合物，它们相互作用以抵消彼此的作用，除非来自一侧的刺激超过另一侧以破坏静止状态。尽管最初认为MMPs严格促进血管生成，但在过去十年中发现了这个蛋白水解家族的新功能，如介导血管消退和产生具有抗血管生成能力的基质片段。这些发现表明MMPs是多方面的促血管生成和抗血管生成效应器。本综述的目的是向读者介绍MMP家族的一般结构和特征，并讨论它们在与血管生成相关的以下关键步骤中的基因表达和酶活性的时空调节：血管基底膜的降解、内皮细胞在相邻ECM内的增殖和侵袭、组织成未成熟的小管、这些新生血管的成熟以及血管网络的修剪和消退。
