A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture.

A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture.
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DOI:
10.1016/j.abb.2014.01.013
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发表时间:
2014-03-01
影响因子:
3.9
通讯作者:
Yamada, Yoshihiko
Yamada, Yoshihiko
中科院分区:
生物学3区
文献类型:
--
作者:
de Vega, Susana;Suzuki, Nobuharu;Nonaka, Risa;Sasaki, Takako;Forcinito, Patricia;Arikawa-Hirasawa, Eri;Yamada, Yoshihiko

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我们以前已经证明,fibulin-7(Fbln 7)是由前成牙本质细胞和成牙本质细胞在牙齿中表达,定位于基底膜和牙本质基质中,是牙齿间充质细胞和成牙本质细胞的粘附分子。Fbln 7也通过内皮细胞在血管中表达。在这份报告中,我们表明,重组的C-末端Fbln 7片段(Fbln 7-C)结合到人脐静脉内皮细胞(HUVECs),但不促进细胞铺展和肌动蛋白应力纤维的形成。Fbln 7-C与HUVECs的结合诱导整合素在细胞粘附位点与其他粘着斑分子聚集,并持续激活FAK、p130 Cas和Rac 1。此外,RhoA活化被抑制,从而防止HUVEC扩散。由于内皮细胞铺展是血管生成的重要步骤,我们使用内皮细胞管形成和血管从主动脉环出芽的体外测定来检查Fbln 7-C对血管生成的影响。我们发现Fbln 7-C在主动脉环试验中抑制HUVEC管形成和血管出芽。我们的研究结果表明Fbln 7 C-末端区域具有潜在的抗血管生成活性。
We have previously demonstrated that fibulin-7 (Fbln7) is expressed in teeth by pre-odontoblast and odontoblast cells, localized in the basement membrane and dentin matrices, and is an adhesion molecule for dental mesenchyme cells and odontoblasts. Fbln7 is also expressed in blood vessels by endothelial cells. In this report, we show that a recombinant C-terminal Fbln7 fragment (Fbln7-C) bound to Human Umbilical Vein Endothelial Cells (HUVECs) but did not promote cell spreading and actin stress fiber formation. Fbln7-C binding to HUVECs induced integrin clustering at cell adhesion sites with other focal adhesion molecules, and sustained activation of FAK, p130Cas, and Rac1. In addition, RhoA activation was inhibited, thereby preventing HUVEC spreading. As endothelial cell spreading is an important step for angiogenesis, we examined the effect of Fbln7-C on angiogenesis using in vitro assays for endothelial cell tube formation and vessel sprouting from aortic rings. We found that Fbln7-C inhibited the HUVEC tube formation and the vessel sprouting in aortic ring assays. Our findings suggest potential anti-angiogenic activity of the Fbln7 C-terminal region.
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