Kozian D H, Ziche M, Augustin H G
Department of Gynecology and Obstetrics, University of Göttingen Medical School, Germany.
Lab Invest. 1997 Feb;76(2):267-76.
Increasing evidence suggests that autocrine endothelial cell activity contributes significantly to the angiogenic cascade once the endothelial cells are initially activated by exogenous stimuli. We have employed the differential RNA-display technique to identify endothelial cell genes that are expressed under autocrine control as a result of the cells' release from growth arrest. Among the differentially expressed genes was the activin-binding and- neutralizing glycoprotein follistatin (FS), which was expressed by migrating endothelial cells and down-regulated once the cells had reached growth arrest. Cytokine exposure identified FS as a basic fibroblast growth factor (bFGF)-inducible gene. In contrast, activin-beta A, an inhibitor of endothelial cell proliferation, was constitutively expressed by migrating and resting endothelial cells. Exogenous recombinant FS induced proliferation of human umbilical vein endothelial cells and low bFGF-expressing bovine aortic endothelial cells. In vivo, FS was moderately angiogenic in the rabbit cornea. However, FS implantation in the cornea in combination with subcritical concentrations of bFGF induced a strong angiogenic response. The data demonstrate that FS by itself and particularly in synergy with bFGF induces angiogenesis. Furthermore, differential expression by endothelial cells suggests a critical role of the FS/activin-beta A system in regulating autocrine endothelial cell activity.
越来越多的证据表明，一旦内皮细胞被外源性刺激最初激活，自分泌内皮细胞活性在血管生成级联反应中起重要作用。我们采用差异RNA显示技术来鉴定在内皮细胞因脱离生长停滞而释放后，在自分泌控制下表达的内皮细胞基因。差异表达基因中包括激活素结合和中和糖蛋白卵泡抑素（FS），它由迁移的内皮细胞表达，一旦细胞达到生长停滞就下调。细胞因子暴露确定FS是一种碱性成纤维细胞生长因子（bFGF）诱导基因。相反，激活素βA，一种内皮细胞增殖抑制剂，由迁移和静止的内皮细胞组成性表达。外源性重组FS诱导人脐静脉内皮细胞和低表达bFGF的牛主动脉内皮细胞增殖。在体内，FS在兔角膜中具有中等程度的血管生成作用。然而，FS与亚临界浓度的bFGF联合植入角膜可诱导强烈的血管生成反应。数据表明，FS自身，特别是与bFGF协同作用可诱导血管生成。此外，内皮细胞的差异表达表明FS/激活素βA系统在调节自分泌内皮细胞活性中起关键作用。
