Lafleur M A, Forsyth P A, Atkinson S J, Murphy G, Edwards D R
School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, England.
Biochem Biophys Res Commun. 2001 Mar 30;282(2):463-73. doi: 10.1006/bbrc.2001.4596.
Angiogenic stimuli selectively induced expression of membrane type-1 matrix metalloproteinase (MT1-MMP) transcripts and protein in human umbilical vein endothelial cells (HUVECs). Pro-MMP-2 activation was blocked by treatment with tissue inhibitor of metalloproteinases-2 (TIMP-2), but not by TIMP-1 or inhibitors of other proteinase classes. Anti-MT1-MMP antibodies abrogated recombinant pro-MMP-2 activation by plasma membranes, indicating that MT1-MMP is the main mediator of pro-MMP-2 activation in HUVECs. Cocultures of HUVECs with smooth muscle cells (SMC) or pericytes (PC) resulted in the suppression of HUVEC pro-MMP-2 activation. Treatment of A10 SMC conditioned media with a neutralising anti-TIMP-2 antibody prevented the suppression of HUVEC pro-MMP-2 activation. Inhibition of HUVEC MT1-MMP function by PC and SM3 SMC correlated with elevated TIMP-3 expression. Thus, perivascular supporting cells regulate the functions of proangiogenic MMPs elaborated by endothelial cells via selective expression of TIMPs. This interplay may be important for maintenance of blood vessel architecture and neovascularisation.
血管生成刺激因子可选择性地诱导人脐静脉内皮细胞（HUVECs）中膜型-1基质金属蛋白酶（MT1-MMP）转录本和蛋白的表达。金属蛋白酶组织抑制剂-2（TIMP-2）处理可阻断前MMP-2的激活，但TIMP-1或其他蛋白酶类抑制剂则不能。抗MT1-MMP抗体可消除质膜对重组前MMP-2的激活作用，表明MT1-MMP是HUVECs中前MMP-2激活的主要介质。HUVECs与平滑肌细胞（SMC）或周细胞（PC）共培养可导致HUVECs前MMP-2激活受到抑制。用中和性抗TIMP-2抗体处理A10 SMC条件培养基可防止HUVECs前MMP-2激活受到抑制。PC和SM3 SMC对HUVECs MT1-MMP功能的抑制与TIMP-3表达升高相关。因此，血管周围支持细胞通过TIMP的选择性表达来调节内皮细胞产生的促血管生成MMP的功能。这种相互作用可能对维持血管结构和新生血管形成很重要。
