Identification of peptides derived from the C-terminal domain of fibulin-7 active for endothelial cell adhesion and tube formation disruption.
Identification of peptides derived from the C-terminal domain of fibulin-7 active for endothelial cell adhesion and tube formation disruption.
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DOI：
10.1002/bip.22754
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发表时间：
2016-03
期刊：
影响因子：
2.9
通讯作者：
Arikawa-Hirasawa E
中科院分区：
文献类型：
--
作者：
de Vega S;Hozumi K;Suzuki N;Nonaka R;Seo E;Takeda A;Ikeuchi T;Nomizu M;Yamada Y;Arikawa-Hirasawa E
尽管已经对病理性血管生成进行了研究，但仍有必要开发针对血管生成相关疾病的新疗法。纤维蛋白-7(Fbln7)是细胞外基质纤维蛋白家族的成员。Fbln7的C末端片段Fbln7-C与内皮细胞结合并抑制其在培养中的管状形成。在这项研究中，我们筛选了12个合成肽，覆盖了Fbln7-C的纤维蛋白球状结构域，以确定内皮细胞黏附的活性部位和体外抗血管生成活性。FC10、FC11和FC12三种多肽均能促进人脐静脉内皮细胞(HUVECs)的黏附，FC10上的HUVECs形态与Fbln7-C上相似。乙二胺四乙酸乙二酯和抗整合素β1功能阻断抗体抑制内皮细胞与FC10和FC12的黏附，肝素抑制HUVECs与FC11和FC12的黏附。FC10和FC11抑制人脐静脉内皮细胞管的形成。我们的结果表明，来自Fbln7-C的三个肽对内皮细胞黏附具有生物活性，并破坏血管形成，这表明这些肽有可能用于血管生成相关疾病的治疗。
Despite the research done on pathological angiogenesis, there is still a need for the development of new therapies against angiogenesis-related diseases. Fibulin-7 (Fbln7) is a member of the extracellular matrix fibulin protein family. The Fbln7 C-terminal fragment, Fbln7-C, binds to endothelial cells and inhibits their tube formation in culture. In this study, we screened 12 synthetic peptides, covering the fibulin-globular domain of Fbln7-C, to identify active sites for endothelial cell adhesion and in vitro anti-angiogenic activity. Three peptides, fc10, fc11, and fc12, promoted Human Umbilical Vein Endothelial Cells (HUVECs) adhesion, and the morphology of HUVECs on fc10 was similar to that on Fbln7-C. EDTA and the anti-integrin β1 function-blocking antibody inhibited HUVECs adhesion to both fc10 and fc12, and heparin inhibited HUVECs adhesion to both fc11 and fc12. fc10 and fc11 inhibited HUVECs tube formation. Our results suggest that three peptides from Fbln7-C are biologically active for endothelial cell adhesion and disrupt the tube formation, suggesting a potential therapeutic use of these peptides for angiogenesis-related diseases.