Paracrine or virus-mediated induction of decorin expression by endothelial cells contributes to tube formation and prevention of apoptosis in collagen lattices
Paracrine or virus-mediated induction of decorin expression by endothelial cells contributes to tube formation and prevention of apoptosis in collagen lattices
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DOI：
10.1016/s0171-9335(99)80006-5
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发表时间：
1999-01-01
影响因子：
6.6
通讯作者：
Kresse, H
中科院分区：
文献类型：
--
作者：
Schönherr, E;O'Connell, BC;Kresse, H
静息的内皮细胞表达小的蛋白聚糖双糖链，而发芽的内皮细胞也合成核心蛋白聚糖，一种相关的蛋白聚糖。在这里，我们表明，核心蛋白聚糖在人肉芽肿组织的内皮细胞中表达。对于体外研究，将人内皮衍生细胞系EA.hy 926在1%胎牛血清存在的情况下在漂浮的胶原蛋白晶格的顶部或内部培养6天或更长时间，所述胶原蛋白晶格也由少量大鼠成纤维细胞填充。内皮细胞排列成索状结构，并形成被人核心蛋白聚糖包围的空腔。在共培养6天和12天后，分别约14%和20%的内皮细胞发生凋亡。然而，在不存在成纤维细胞的情况下，12天后细胞凋亡的程度为约60%，并且没有形成索状结构，也不能诱导核心蛋白聚糖的产生。当由EA.hy926细胞填充的晶格在以下条件之一下维持时也是这种情况：1）10%胎牛血清; 2）成纤维细胞条件培养基; 3）外源性核心蛋白聚糖;或4）用已知参与血管生成的单个生长因子处理。成纤维细胞诱导EA.hy 926细胞中血管生成表型的机制尚不清楚，但通过使用复制缺陷型腺病毒将人核心蛋白聚糖cDNA转导到EA.hy 926细胞中，提出了核心蛋白聚糖表达和内皮细胞表型之间的因果关系。当转导的细胞在胶原晶格中培养时，毛细血管样结构的形成不需要成纤维细胞，并且细胞凋亡减少。因此。核心蛋白聚糖的表达似乎对于EA.hy926细胞的存活以及对于该血管生成模型中的索和管形成特别重要。
Resting endothelial cells express the small proteoglycan biglycan, whereas sprouting endothelial cells also synthesize decorin, a related proteoglycan, Here we show that decorin is expressed in endothelial cells in human granulomatous tissue. For in vitro investigations, the human endothelium-derived cell line, EA.hy 926, was cultured for 6 or more days in the presence of 1% fetal calf serum on top of or within floating collagen lattices which were also populated by a small number of rat fibroblasts. Endothelial cells aligned in cord-like structures and developed cavities that were surrounded by human decorin, About 14% and 20 % of endothelial cells became apoptotic after 6 and 12 days of co-culture, respectively. In the absence of fibroblasts, however, the extent of apoptosis was about 60 % after 12 days, and cord-like structures were not formed nor could decorin production be induced. This was also the case when lattices populated by EA.hy 926 cells were maintained under one of the Following conditions: 1) 10 % fetal calf serum; 2) fibroblast-conditioned media; 3) exogenous decorin; or 4) treatment with individual growth factors known to be involved in angiogenesis. The mechanism(s) by which fibroblasts induce an angiogenic phenotype in EA.hy 926 cells is (are) not known, but a causal relationship between decorin expression and endothelial cell phenotype was suggested by transducing human decorin cDNA into EA.hy 926 cells using a replication-deficient adenovirus. When the transduced cells were cultured in collagen lattices, there was no requirement of fibroblasts for the formation of capillary-like structures and apoptosis was reduced. Thus. decorin expression seems to be of special importance for the survival of EA.hy 926 cells as well as for cord and tube formation in this angiogenesis model.