Wong A L, Haroon Z A, Werner S, Dewhirst M W, Greenberg C S, Peters K G
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Circ Res. 1997 Oct;81(4):567-74. doi: 10.1161/01.res.81.4.567.
Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a critical process during early development. However, angiogenesis rarely occurs in the adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in response to injury, and in response to pathological conditions such as tumorigenesis and diabetes mellitus. Tie2 (also known as Tek) is a novel endothelium-specific receptor tyrosine kinase, which has been demonstrated to be essential for the development of the embryonic vasculature; Tie2 knockout mice die by embryonic day 10.5 with specific defects in the formation of microvessels. Tie2 is downregulated later in embryogenesis, and its function in the adult has been relatively unexplored. To gain insight into the potential functions of Tie2 in the adult vasculature, Tie2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. Tie2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing skin wounds. Immunoprecipitation and RNase protection assay demonstrated upregulation of Tie2 protein and mRNA in rat and mouse skin wounds, respectively. Moreover, Tie2 immunoprecipitated from skin wounds was tyrosine-phosphorylated, indicating active downstream signaling. Surprisingly, Tie2 was also expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues, and Tie2 immunoprecipitated from quiescent adult tissues was also tyrosine-phosphorylated. Together, these results suggest a dual function for Tie2 in adult tissues involving both angiogenesis and vascular maintenance.
血管生成是指新血管从现有脉管系统中萌芽生长的过程，是早期发育过程中的一个关键过程。然而，血管生成在成体中很少发生，除非是对卵巢和子宫的周期性激素刺激、损伤以及肿瘤发生和糖尿病等病理状况做出反应。Tie2（也称为Tek）是一种新型的内皮细胞特异性受体酪氨酸激酶，已被证明对胚胎脉管系统的发育至关重要；Tie2基因敲除小鼠在胚胎第10.5天死亡，微血管形成存在特定缺陷。Tie2在胚胎发育后期表达下调，其在成体中的功能相对未被充分研究。为了深入了解Tie2在成体脉管系统中的潜在功能，研究人员检测了Tie2在经历血管生成的成体组织和静止组织中的表达情况。通过免疫组织化学方法将Tie2的表达定位到在激素刺激的卵泡成熟和子宫发育过程中以及愈合的皮肤伤口中经历血管生成的大鼠组织中新血管的内皮细胞上。免疫沉淀和核糖核酸酶保护试验分别证明了大鼠和小鼠皮肤伤口中Tie2蛋白和mRNA的上调。此外，从皮肤伤口免疫沉淀得到的Tie2发生了酪氨酸磷酸化，表明下游信号传导活跃。令人惊讶的是，Tie2在多种成体组织的整个静止脉管系统（动脉、静脉和毛细血管）中也有表达，并且从静止成体组织中免疫沉淀得到的Tie2也发生了酪氨酸磷酸化。这些结果共同表明，Tie2在成体组织中具有涉及血管生成和血管维持的双重功能。
