Molecular balance of capillary tube formation versus regression in wound repair: Role of matrix metalloproteinases and their inhibitors
Molecular balance of capillary tube formation versus regression in wound repair: Role of matrix metalloproteinases and their inhibitors
复制标题
DOI：
10.1038/sj.jidsymp.5650008
复制
发表时间：
2006-09-01
影响因子：
--
通讯作者：
Saunders, W. Brian
中科院分区：
文献类型：
--
作者：
Davis, George E.;Saunders, W. Brian
在这篇综述中，我们讨论了不同的基质金属蛋白酶（MMPs）及其抑制剂，差异控制的过程中的毛细管形成（形态发生）与毛细管回归三维（3D）胶原蛋白基质的识别。这项工作直接涉及创面修复过程中肉芽组织的形成和消退。膜金属蛋白酶，MT 1-MMP（MMP-14），是所需的内皮细胞（EC）管的形成使用体外试验，模拟血管生成或血管生成发芽在三维胶原基质。这些事件被EC中MT 1-MMP的小干扰RNA（siRNA）抑制或通过加入金属蛋白酶组织抑制剂（TIMP）-2、-3和-4而不是TIMP-1显著阻断。相比之下，MMP-1和MMP-10在EC管形成期间被强烈诱导以调节管消退（在被丝氨酸蛋白酶激活之后）而不是形成的过程。选择性抑制可溶性MMP的TIMP-1通过抑制MMP-1和MMP-10阻断管腔退化，而对EC管腔形成没有影响。MMP-1和MMP-10的siRNA抑制显著阻断管消退而不影响管形成。此外，我们还讨论了在我们的模型系统中，周细胞诱导的EC管网稳定似乎是通过EC衍生的TIMP-2和周细胞衍生的TIMP-3来阻止毛细管形成和回归途径。
In this review, we discuss the identification of distinct matrix metalloproteinases (MMPs) and their inhibitors that differentially control the processes of capillary tube formation (morphogenesis) versus capillary tube regression in three-dimensional (3D) collagen matrices. This work directly relates to both granulation tissue formation and regression during wound repair. The membrane metalloproteinase, MT1-MMP (MMP-14), is required for endothelial cell (EC) tube formation using in vitro assays that mimic vasculogenesis or angiogenic sprouting in 3D collagen matrices. These events are markedly blocked by small interfering RNA (siRNA) suppression of MT1-MMP in ECs or by addition of tissue inhibitor of metalloproteinases (TIMPs)-2,-3, and -4 but not TIMP-1. In contrast, MMP-1 and MMP-10 are strongly induced during EC tube formation to regulate the process of tube regression (following activation by serine proteases) rather than formation. TIMP-1, which selectively inhibits soluble MMPs, blocks tube regression by inhibiting MMP-1 and MMP-10 while having no influence on EC tube formation. siRNA suppression of MMP-1 and MMP-10 markedly blocks tube regression without affecting tube formation. Furthermore, we discuss that pericyte-induced stabilization of EC tube networks in our model system appears to occur through EC-derived TIMP-2 and pericyte-derived TIMP-3 to block both the capillary tube formation and regression pathways.