Stetler-Stevenson William G, Seo Dong-Wan
Cell & Cancer Biology Branch, Vascular Biology Faculty, CCR, NCI, NIH, Bldg. 10, Room 2A33, MSC# 1500, 10 Center Dr., Bethesda, MD 20892-1500, USA.
Trends Mol Med. 2005 Mar;11(3):97-103. doi: 10.1016/j.molmed.2005.01.007.
Remodeling of the extracellular matrix--regulated by the matrix metalloproteinases (MMPs) and their endogenous inhibitors--is an important component of disease progression in many chronic disease states. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury, such as angiogenesis. The tissue inhibitors of metalloproteinases (TIMPs) have been shown to regulate MMP activity. However, recent findings demonstrate that an MMP-independent effect of TIMP-2 inhibits the mitogenic response of human microvascular endothelial cells to growth factors. This is the first demonstration of a cell-surface signaling receptor for a member of the TIMP family and suggests that TIMP-2 functions to regulate cellular responses to growth factors. These new findings are integrated in a comprehensive model of TIMP-2 function in tissue homeostasis.
细胞外基质重塑——由基质金属蛋白酶（MMPs）及其内源性抑制剂调控——是许多慢性疾病状态下疾病进展的重要组成部分。不受控制的MMP活性可导致显著的组织损伤，促进疾病进展，并与宿主对病理性损伤的反应相关，如血管生成。金属蛋白酶组织抑制剂（TIMPs）已被证明可调节MMP活性。然而，最近的研究结果表明，TIMP-2的非MMP依赖性作用可抑制人微血管内皮细胞对生长因子的促有丝分裂反应。这是首次证明TIMP家族成员存在细胞表面信号受体，并表明TIMP-2具有调节细胞对生长因子反应的功能。这些新发现被整合到一个关于TIMP-2在组织稳态中功能的综合模型中。
