BASIC FIBROBLAST GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 - SYNERGISTIC MEDIATORS OF ANGIOGENESIS IN-VITRO
BASIC FIBROBLAST GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 - SYNERGISTIC MEDIATORS OF ANGIOGENESIS IN-VITRO
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DOI：
10.1002/jcp.1041570118
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发表时间：
1993-10-01
影响因子：
5.6
通讯作者：
MAYBERG, MR
中科院分区：
文献类型：
--
作者：
GAJDUSEK, CM;LUO, ZG;MAYBERG, MR
我们使用二维培养皿培养物和三维水合胶原凝胶研究了碱性成纤维细胞生长因子（bFGF）和转化生长因子β-1（TGF-b）对牛主动脉内皮细胞有丝分裂和形态发生的相对作用。 bFGF 单独刺激内皮细胞增殖，EC50 为 0.5 ng/ml。当 bFGF 水平大于 2.5 ng/ml 时，汇合单层细胞的形态变化占主导地位；细胞从鹅卵石形态转变为细长的细胞模式，并显示出向培养皿裸露区域的迁移增强。在三维模型中，将内皮细胞单层暴露于高水平的bFGF会刺激小细胞直接迁移到单层之下，但不会侵入凝胶基质。与 bFGF 联合使用时，肝素可增强形态发生变化，但不会增强有丝分裂。通过在二维培养物中响应0.5ng/ml TGF-b和10-20ng/ml bFGF诱导内皮细胞发芽，证明了bFGF在汇合培养物中对TGF-b的抗增殖作用的修饰。在胶原凝胶上，内皮细胞以剂量依赖性方式迁移到凝胶深层：0.3-0.7 ng/ml TGF-b 时侵袭最大，浓度较高时侵袭减弱。支持细胞侵袭的最佳胶原浓度为0.075%胶原，随着胶原凝胶密度的增加，侵袭细胞的数量减少。通过扫描电子显微镜，入侵的内皮细胞呈现出具有细长细胞延伸的成纤维细胞样外观。我们得出结论，bFGF 和 TGF-b 对培养物中的内皮细胞形态和有丝分裂具有独立的影响。这些药物以特定剂量组合，可刺激二维模型中的发芽和胶原凝胶模型中的细胞侵袭。形态发生变化可能是决定血管生成的主要事件。 (C) 1993 Wiley-Liss, Inc.
We investigated the relative roles of basic fibroblast growth factor (bFGF) and transforming growth factor beta-1 (TGF-b) on bovine aortic endothelial cell mitogenesis and morphogenesis using two-dimensional Petri dish cultures and a three-dimensional hydrated collagen gel. bFGF alone stimulated endothelial cell proliferation with an EC50 of 0.5 ng/ml. At bFGF levels greater than 2.5 ng/ml, morphologic alterations in confluent monolayers predominated; cells changed from a cobblestone morphology to an elongated cell pattern and showed enhanced migration into a denuded area of a Petri dish. In the three-dimensional model, exposure of endothelial cell monolayers to high bFGF levels stimulated minor cell migration directly under the monolayer but no invasion into the gel matrix. In combination with bFGF, heparin potentiated morphogenic changes, but not mitogenesis. bFGF modification of the antiproliferative effect of TGF-b in confluent cultures was evidenced by induction of endothelial cell sprouting in response to 0.5 ng/ml TGF-b and 10-20 ng/ml bFGF in two-dimensional cultures. On collagen gels, endothelial cells migrated into the deep layers of the gel in a dose-dependent manner: invasion was maximal at 0.3-0.7 ng/ml TGF-b with decreased invasion at higher concentrations. The optimal collagen concentration that supported cell invasion was 0.075% collagen with the number of invading cells decreasing with increasing collagen gel density. By scanning electron microscopy, invading endothelial cells assumed a fibroblast-like appearance with slender cell extensions. We concluded that bFGF and TGF-b had independent effects on endothelial cell morphology and mitogenesis in culture. In combination at specific doses, these agents stimulated sprouting in the two-dimensional model and cell invasion in a collagen gel model. Morphogenic changes may be the primary event in determining angiogenesis. (C) 1993 Wiley-Liss, Inc.