Protein kinase Bα/Akt1 regulates placental development and fetal growth
Protein kinase Bα/Akt1 regulates placental development and fetal growth
复制标题
DOI：
10.1074/jbc.m302847200
复制
发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Hemmings, BA
中科院分区：
文献类型：
--
作者：
Yang, ZZ;Tschopp, O;Hemmings, BA
蛋白激酶Balpha（PKB alpha/Akt 1）参与代谢、转录、细胞存活、血管生成、细胞迁移、生长和肿瘤发生的调节。先前，据报道，PKBa缺陷型小鼠较小，新生儿死亡率增加（Cho，H.，Thorvaldsen，J.L.，Chu，Q.，Feng，F.，中国农业科学院，Birnbaum，M. J.（2001）J. Biol. Chem. 276，38349 - 38352和Chen，W.美国，Xu，P. Z.，Gottlob，K.，Chen，M. L.，索科尔，K.，Shiyanova，T.，罗宁森岛Wenig，W.，Suzuki，R.，Tobe，K.，Kadowaki，T.，和Hay，N.（2001）Genes Dev. 15，22032208）。我们发现，PKB α在胎盘中广泛表达，包括所有类型的滋养层细胞和血管内皮细胞。Pkbalpha（-/-）胎盘显示明显的萎缩，蜕膜基底层明显减少，海绵滋养层中含糖原细胞几乎完全丧失，血管形成减少。Pkbalpha（-/-）胎盘也显示PKB和内皮一氧化氮合酶的磷酸化显著降低。这些缺陷可能导致胎盘功能不全、胎儿生长障碍和新生儿死亡。这些数据代表了PKB α和内皮一氧化氮合酶在调节胎盘发育中的作用的第一个证据，并提供了宫内生长迟缓的动物模型。
Protein kinase Balpha (PKBalpha/Akt1) is implicated in the regulation of metabolism, transcription, cell survival, angiogenesis, cell migration, growth, and tumorigenesis. Previously, it was reported that PKBalpha-deficient mice are small with increased neonatal mortality (Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., and Birnbaum, M. J. ( 2001) J. Biol. Chem. 276, 38349 - 38352 and Chen, W. S., Xu, P. Z., Gottlob, K., Chen, M. L., Sokol, K., Shiyanova, T., Roninson, I., Wenig, W., Suzuki, R., Tobe, K., Kadowaki, T., and Hay, N. ( 2001) Genes Dev. 15, 2203 2208). Here we show that PKBalpha is widely expressed in placenta including all types of trophoblast and vascular endothelial cells. Pkbalpha(-/-) placentae display significant hypotrophy, with marked reduction of the decidual basalis and nearly complete loss of glycogen-containing cells in the spongiotrophoblast, and exhibit decreased vascularization. Pkbalpha(-/-) placentae also show significant reduction of phosphorylation of PKB and endothelial nitric-oxide synthase. These defects may cause placental insufficiency, fetal growth impairment, and neonatal mortality. These data represent the first evidence for the role of PKBalpha and endothelial nitric-oxide synthase in regulating placental development and provide an animal model for intrauterine growth retardation.