Wright M, Aikawa M, Szeto W, Papkoff J
Valentis Corporation, 863A Mitten Road, Burlingame, California, 94010, USA.
Biochem Biophys Res Commun. 1999 Sep 24;263(2):384-8. doi: 10.1006/bbrc.1999.1344.
The beta-catenin signal transduction pathway, which can be activated by secreted Wnt proteins, plays a key role in normal embryonic development and in malignant transformation of the mammary gland and colon. Here we demonstrate, for the first time, that Wnt and beta-catenin signaling also function in cells of the vasculature. RT-PCR analysis showed that primary endothelial and smooth muscle cell cultures, of both mouse and human origin, express members of the Wnt and Wnt receptor (Frizzled) gene families. Transfection of an expression vector for Wnt-1 into primary endothelial cells increased both the free pool of beta-catenin and the transcription from a Lef/tcf-dependent reporter gene construct. Expression of Wnt-1, but not Wnt-5a, also stimulated proliferation of primary endothelial cell cultures. These data show that Wnt and Frizzled proteins can regulate signal transduction, via beta-catenin, in endothelial cells. These findings suggest that Wnt signaling may feature in normal differentiation of the vasculature as well as in pathological settings where endothelial and smooth muscle proliferation is disturbed.
β-连环蛋白信号转导通路可被分泌型Wnt蛋白激活，在正常胚胎发育以及乳腺和结肠的恶性转化过程中发挥关键作用。在此，我们首次证明Wnt和β-连环蛋白信号传导在脉管系统细胞中也发挥作用。逆转录聚合酶链反应（RT-PCR）分析表明，源自小鼠和人类的原代内皮细胞和平滑肌细胞培养物表达Wnt和Wnt受体（卷曲蛋白）基因家族的成员。将Wnt-1表达载体转染到原代内皮细胞中，可增加β-连环蛋白的游离池以及来自Lef/tcf依赖性报告基因构建体的转录。Wnt-1而非Wnt-5a的表达也刺激了原代内皮细胞培养物的增殖。这些数据表明，Wnt和卷曲蛋白可通过β-连环蛋白调节内皮细胞中的信号转导。这些发现提示，Wnt信号传导可能在脉管系统的正常分化以及内皮细胞和平滑肌细胞增殖受到干扰的病理情况下发挥作用。
