Wnt/β-catenin signaling induces proliferation, survival and Interleukin-8in human endothelial cells
Wnt/β-catenin signaling induces proliferation, survival and Interleukin-8in human endothelial cells
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DOI：
10.1007/s10456-005-5612-9
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发表时间：
2005-01-01
期刊：
影响因子：
9.8
通讯作者：
Kitajewski, Jan
中科院分区：
文献类型：
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作者：
Masckauchan, T. Nestor H.;Shawber, Carrie J.;Kitajewski, Jan
蛋白质是能够控制多种生物过程如细胞分化和增殖的分泌信号蛋白。许多Wnt通过典型的β-连环蛋白信号通路起作用。在这里，我们报告说，Wnt受体和转录效应表达在原代人内皮细胞和Wnt/β-连环蛋白信号促进血管生成。人脐静脉和微血管内皮细胞I表达Wnt受体，卷曲蛋白-4，-5，-6，和β-连环蛋白相关转录因子，Tcf-1，-3，-4和Lef-1。在内皮细胞中，Wnt-1的异位表达稳定了胞质β-连环蛋白，证明了Wnt/β-连环蛋白经典信号通路的激活。Wnt-1或β-连环蛋白的稳定和活性形式β-连环蛋白S37 A的表达促进内皮细胞增殖。在bFGF存在下，Wnt/β-连环蛋白信号传导诱导的增殖是最佳的。β-连环蛋白S37 A在内皮细胞中的表达促进生长因子剥夺后的存活。使用matrigel分析，Wnt-1或β-cateninS 37 A的表达促进了毛细血管样网络的形成。为了帮助定义Wnt血管生成功能的效应物，使用微阵列分析来比较表达Wnt-1的内皮细胞与对照细胞。白细胞介素-8是一种已知的血管生成因子，被鉴定为内皮细胞中Wnt/β-连环蛋白信号转导的转录靶点。Wnt-1或β-连环蛋白S37 A的表达诱导白细胞介素-8转录和分泌蛋白。因此，我们得出结论，Wnt/β-连环蛋白信号可能通过诱导已知的血管生成调节因子如白细胞介素-8来促进血管生成。
Writs are secreted signaling proteins able to control diverse biological processes such as cell differentiation and proliferation. Many Wnts act through a canonical, beta-catenin signaling pathway. Here, we report that Wnt receptors and transcriptional effectors are expressed in primary human endothelial cells and that Wnt/beta-catenin signaling promotes angio genesis. Human umbilical vein and microvascular endothelia I cells express Wnt receptors, Frizzled-4, -5, -6, and beta-catenin-associated transcription factors, Tcf-1, -3, -4 and Lef-1. In endothelial cells, ectopic expression of Wnt-1 stabilized cytosolic beta-catenin, demonstrating activation of the Wnt/beta-catenin canonical signaling pathway. Expression of Wnt-1 or a stabilized and active form of beta-catenin, beta-cateninS37A, promoted endothelial cell proliferation. Proliferation induced by Wnt/beta-catenin signaling was optimal in the presence of bFGF. beta-cateninS37A expression in endothelial cells promoted survival after growth factor deprivation. Using matrigel assays, Wnt-1 or beta-cateninS37A expression promoted the formation of capillary-like networks. To help define the effectors of Wnt angiogenic function, microarray analysis was used to compare endothelial cells expressing Wnt-1 to control cells. Interleukin-8, a known angiogenic factor, was identificd as a transcriptional target of Wnt/beta-catenin signaling in endothelial cells. Expression of either Wnt-1 or beta-cateninS37A induced Interleukin-8 transcripts and secreted protein. We thus conclude that Wnt/beta-catenin signaling promotes angiogenesis possibly via the induction of known angiogenic regulators such as Interleukin-8.