INHIBITION OF ANGIOGENESIS BY TISSUE INHIBITOR OF METALLOPROTEINASE
INHIBITION OF ANGIOGENESIS BY TISSUE INHIBITOR OF METALLOPROTEINASE
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DOI：
10.1002/jcp.1041600122
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发表时间：
1994-07-01
影响因子：
5.6
通讯作者：
POLVERINI, PJ
中科院分区：
文献类型：
--
作者：
JOHNSON, MD;KIM, HRC;POLVERINI, PJ
基质蛋白酶在细胞侵袭和迁移中起关键作用，包括血管生成过程。特异性因子诱导血管生成反应的能力与其刺激基质蛋白酶合成和释放相关。使用体内血管生成试验，已知的血管生成因子，碱性成纤维细胞生长因子（bFGF）和脂肪细胞条件培养基的内皮细胞反应，被阻断的基质金属蛋白酶活性，TIMP-1的抑制剂。TIMP效应至少部分通过抑制内皮细胞迁移来介导，如通过Boyden室测定中TIMP阻断趋化性的能力所确定的。这些结果表明，抑制迁移是对内皮细胞的直接作用，不需要辅助细胞。另一个观察结果是，与未分化的F442 A对照相比，TIMP的RNA水平在分化的脂肪细胞中显著降低。因此，血管生成表型的获得可能不仅涉及阳性因子的诱导，还涉及血管生成抑制剂的抑制。(C)1994 Wiley-Liss，Inc.
Matrix proteases play a critical role in cell invasion and migration, including the process of angiogenesis. The ability of specific factors to induce angiogenic responses correlates with their stimulation of matrix protease synthesis and release. Using an in vivo angiogenesis assay, the endothelial cell response to known angiogenic factors, basic fibroblast growth factor (bFGF) and adipocyte conditioned medium, was blocked by an inhibitor of matrix metalloproteinase activity, TIMP-1. The TIMP effect was mediated, at least in part, through the inhibition of endothelial cell migration, as determined by the ability of TIMP to block chemotaxis in a Boyden chamber assay. These results indicate that the inhibition of migration is a direct effect on the endothelial cells and does not require accessory cells. An additional observation was that the RNA levels for TIMP were significantly reduced in differentiated adipocytes, compared to undifferentiated F442A controls. Therefore, the acquisition of an angiogenic phenotype may involve not only the induction of positive factors, but also the suppression of angiogenesis inhibitors. (C) 1994 Wiley-Liss, Inc.