Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity
Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity
复制标题
DOI：
10.1006/bbrc.2001.4596
复制
发表时间：
2001-03-30
影响因子：
3.1
通讯作者：
Edwards, DR
中科院分区：
文献类型：
--
作者：
Lafleur, MA;Forsyth, PA;Edwards, DR
血管生成刺激选择性诱导人脐静脉内皮细胞 (HUVEC) 中膜 1 型基质金属蛋白酶 (MT1-MMP) 转录物和蛋白质的表达。 Pro-MMP-2 的激活可被金属蛋白酶组织抑制剂 2 (TIMP-2) 阻断，但不能被 TIMP-1 或其他蛋白酶类抑制剂阻断。抗 MT1-MMP 抗体消除了质膜对重组 pro-MMP-2 的激活，表明 MT1-MMP 是 HUVEC 中 pro-MMP-2 激活的主要介质。 HUVEC 与平滑肌细胞 (SMC) 或周细胞 (PC) 的共培养导致 HUVEC pro-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 HUVEC pro-MMP-2 激活的抑制。 PC 和 SM3 SMC 对 HUVEC 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选择性表达 TIMP 来调节内皮细胞产生的促血管生成 MMP 的功能。这种相互作用对于维持血管结构和新血管形成可能很重要。 (C) 2001 年学术出版社。
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. (C) 2001 Academic Press.