Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis
Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis
复制标题
DOI：
10.1038/labinvest.3700476
复制
发表时间：
2006-11-01
影响因子：
5
通讯作者：
Kanai, Yoshikatsu
中科院分区：
文献类型：
--
作者：
Wakui, Shin;Yokoo, Kiyofumi;Kanai, Yoshikatsu
内皮细胞和周细胞在血管生成中发挥着关键作用，血管生成部分由血管生成素 (Ang)/Tie-2 系统和血管内皮生长因子 (VEGF) 控制。在这里，我们研究了内皮细胞和周细胞叉指 (EPI) 内的 Ang、Tie-2 和 VEGF 表达，EPI 由周细胞的细胞质投射和相应的内皮凹痕组成。将热可逆凝胶聚合物盘植入大鼠皮下后，毛细血管密度在第5天较低，在第7天增加至峰值，然后在第10-20天下降。第5天观察到少量EPI，然后在第10天急剧增加至峰值，但在第20天有所下降。光镜和电镜免疫组织化学和RNA原位杂交分析显示，Tie-2定位于内皮细胞，Ang-2定位于内皮细胞和周细胞，而Ang-1和VEGF定位于周细胞，Ang-1在EPI处观察到最强烈。周细胞。常规定量RT-PCR和Western blot分析显示，Ang-1水平在第5-7天较低，然后在第10-20天上升，而VEGF水平在第5-10天较高，但在第20天下降。Ang-2水平仍然很高，Tie-2在第5-20天仍保持在对照水平。本研究表明，血管生成期可能由Ang-2和VEGF的增加启动，而微血管成熟期可能由Ang-1的相对增加和VEGF的减少启动。此外，EPI 可能作为 Ang-1/Tie-2 系统的途径，其中 VEGF 促进周细胞募集以保持微血管完整性。
Endothelial cells and pericytes play critical role in angiogenesis, which is controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular endothelial growth factor (VEGF). Here, we investigated Ang, Tie-2, and VEGF expression within endothelial cells and pericyte interdigitations (EPI), which consist of cytoplasmic projections of pericytes and corresponding endothelial indentations. After subcutaneous implantation of a thermoreversible gelation polymer disc in rats, the capillary density was low on day 5, increased to a peak on day 7, and then decreased on days 10-20. A small number of EPI were observed on day 5, then increased sharply to a peak on day 10, but had decreased on day 20. Light and electron microscopy immunohistochemical and RNA in situ hybridization analyses revealed that Tie-2 localized at endothelial cells, and Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF localized at pericytes, and Ang-1 was most intensely observed at EPI of pericytes. Conventional quantitative RT-PCR and Western blot analyses revealed that the level of Ang-1 was low on days 5-7, then increased on days 10-20, while the level of VEGF was high on days 5-10, but had decreased on day 20. The level of Ang-2 remained high and Tie-2 remained at the level of the control on days 5-20. The present study showed that the angiogenic phase might be initiated by increases in Ang-2 and VEGF, while the microvessel maturation phase might be initiated by a relative increase in Ang-1 and a decrease in VEGF. Moreover, EPI might serve as a pathway for the Ang-1/Tie-2 system, with VEGF promoting pericyte recruitment for microvascular integrity.