Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61).
Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61).
复制标题
DOI：
10.1023/a:1023823803510
复制
发表时间：
2002-01-01
期刊：
影响因子：
9.8
通讯作者：
Brigstock, David R.
中科院分区：
文献类型：
--
作者：
Brigstock, David R.
结缔组织生长因子（CTGF）和富含半胱氨酸的61（CYR 61）是CCN家族的原型成员，CCN家族还包含肾母细胞瘤过表达（NOV）和Wnt诱导的分泌蛋白-1、-2和-3（WISP-1、-2、-3）。这些蛋白质作为细胞外基质（ECM）相关的信号分子起作用，所述信号分子含有允许它们与细胞周围环境中的其他部分直接结合的结构模块。尽管已经鉴定了CCN蛋白的多种靶细胞类型，但有强有力的证据支持CTGF和CYR 61在调节内皮细胞功能和血管生成中的作用。CTGF和CYR 61都可以促进体外内皮细胞的生长、迁移、粘附和存活，并且这些作用中的至少一些是通过细胞表面整合素介导的。这两种蛋白质在内皮细胞中响应于碱性成纤维细胞生长因子（bFGF）或血管内皮生长因子（VEGF）而被转录激活，并且体外内皮细胞增殖和迁移通过CTGF产生或作用的拮抗剂而降低。CTGF和CYR 61在血管内皮细胞中的原位表达模式支持这些分子在正常内皮稳态中的作用，以及参与胚胎发育、胎盘形成、肿瘤形成、纤维化和伤口愈合期间的血管生成过程。CTGF或CYR 61敲除小鼠在胚胎发生和胎儿发育期间表现出血管缺陷。CTGF和CYR 61在血管生成活性的体内测定中都是固有活性的。然而，它们还可以调节其他血管生成分子（例如bFGF、VEGF）以及影响ECM的完整性或稳定性的分子（例如胶原、基质金属蛋白酶（MMP）、MMP的组织抑制剂（TIMP））的产生和/或活性。因此，CTGF和CYR 61通过其作为成纤维细胞或平滑肌细胞等细胞产物的旁分泌作用，或通过其作为内皮细胞产物的自分泌作用，参与多种直接和间接机制，通过这些机制在多个控制点调节血管生成。
Connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61) are prototypical members of the CCN family which also contains nephroblastoma overexpressed (NOV) and Wnt-induced secreted proteins-1, -2 and -3 (WISP-1, -2, -3). These proteins function as extracellular matrix (ECM)-associated signaling molecules that contain structural modules allowing them to bind directly with other moieties in the pericellular environment. Although multiple target cell types have been identified for CCN proteins, there is strong evidence supporting a role for CTGF and CYR61 in the regulation of endothelial cell function and angiogenesis. Both CTGF and CYR61 can promote endothelial cell growth, migration, adhesion and survival in vitro and at least some of these effects are mediated through cell surface integrins. Both proteins are transcriptionally activated in endothelial cells in response to basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF), and endothelial cell proliferation and migration in vitro is reduced by antagonists of CTGF production or action. The expression pattern of CTGF and CYR61 in endothelial cells of vessels in situ supports a role for these molecules in normal endothelial homeostasis, as well as participating in the angiogenic process during embryonic development, placentation, tumor formation, fibrosis, and wound healing. CTGF or CYR61 knockout mice exhibit vascular defects during embryogenesis and fetal development. Both CTGF and CYR61 are intrinsically active in in vivo assays for angiogenic activity. However, they can also regulate the production and/or activity of other angiogenic molecules (e.g. bFGF, VEGF) as well molecules that affect the integrity or stability of the ECM (e.g. collagen, matrix metalloproteases (MMPs), tissue inhibitors of MMPs (TIMPs)). Therefore, through their paracrine action as products of cells such as fibroblasts or smooth muscle cells or through their autocrine action as products of endothelial cells, CTGF and CYR61 participate in a variety of direct and indirect mechanisms by which angiogenesis is regulated at multiple control points.