Nagashima H, Okada M, Hidai C, Hosoda S, Kasanuki H, Kawana M
Department of Cardiology, Heart Institute of Japan, Tokyo Women's Medical College, Japan.
Heart Vessels. 1997;Suppl 12:110-2.
Angiogenesis plays an important role in various diseases and conditions such as malignant tumor, wound healing, and atherosclerosis. Since cell-to-cell adhesion may play a key role in angiogenesis, we investigated the effect of the cadherin-catenin-cytoskeleton complex on angiogenesis in human umbilical vein endothelial cells (HUVECs). Immunofluorescence staining revealed that alpha-catenin, beta-catenin, and plakoglobin were concentrated at cell-cell contacts in HUVECs. Antisense oligonucleotide (AS-oligo), complementary to the region of human plakoglobin was dissolved in saline and applied to the media at 1 mM every 12 h for 4 days, and sense oligonucleotide (S-oligo) was used as control. HUVEC migration from an injury line was enhanced by AS-oligo. Interestingly, HUVECs migrated in line with S-oligo, and in a scattered fashion with AS-oligo. Tube formation on Matrigel occurred earlier with AS-oligo than with S-oligo. These findings indicate that plakoglobin inhibited HUVEC migration and tube formation (angiogenesis) by regulating cell-cell adhesion.
血管生成在多种疾病和病症中发挥着重要作用，如恶性肿瘤、伤口愈合和动脉粥样硬化。由于细胞间黏附可能在血管生成中起关键作用，我们研究了钙黏蛋白 - 连环蛋白 - 细胞骨架复合物对人脐静脉内皮细胞（HUVECs）血管生成的影响。免疫荧光染色显示，α - 连环蛋白、β - 连环蛋白和桥粒斑珠蛋白集中在HUVECs的细胞 - 细胞接触部位。将与人桥粒斑珠蛋白区域互补的反义寡核苷酸（AS - 寡核苷酸）溶解于盐水中，每12小时以1 mM的浓度加入培养基中，持续4天，并使用正义寡核苷酸（S - 寡核苷酸）作为对照。AS - 寡核苷酸增强了HUVEC从损伤线处的迁移。有趣的是，HUVECs与S - 寡核苷酸一起呈线性迁移，而与AS - 寡核苷酸一起呈分散状迁移。在基质胶上形成管腔的过程中，AS - 寡核苷酸比S - 寡核苷酸更早出现。这些发现表明，桥粒斑珠蛋白通过调节细胞 - 细胞黏附来抑制HUVEC迁移和管腔形成（血管生成）。
