EMBL Mouse Biology Unit, Campus A. Buzzati-Traverso, Monterotondo-Scalo (RM), Italy.
Dev Dyn. 2010 Aug;239(8):2149-60. doi: 10.1002/dvdy.22345.
The unquestionable importance of the cardiovascular system for pre- and postnatal life has prompted dissection of the molecular mechanisms underlying its development. Serum and glucocorticoid-inducible kinase 1 (SGK1) is a serine/threonine kinase lying downstream of the phosphoinositide 3 (PI3) kinase pathway, whose embryonic function remains unknown. Here, we show that disruption of Sgk1 in the mouse C57BL/6J genetic background leads to embryonic lethality at embryonic day 10.5-11.5 due to severe embryonic and extraembryonic angiogenic defects and to impaired myocardial trabeculation. Absence of SGK1 results in increased apoptosis of endothelial cells, and of vascular smooth muscle cells highlighting a prosurvival role for SGK1 during angiogenesis. Sgk1 null embryos also display reduced expression levels of Notch signaling genes and decreased expression of the arterial markers Efnb2 and Nrp1. These findings uncover a novel and essential function for SGK1 in cardiovascular development contributing to a better understanding of mammalian angiogenesis.
心血管系统对于产前和产后生命的重要性不言而喻，这促使人们对其发育的分子机制进行了解剖。血清和糖皮质激素诱导激酶 1（SGK1）是一种丝氨酸/苏氨酸激酶，位于磷酸肌醇 3（PI3）激酶途径的下游，其胚胎功能尚不清楚。在这里，我们表明，在 C57BL/6J 遗传背景的小鼠中破坏 Sgk1 会导致胚胎致死，发生在胚胎第 10.5-11.5 天，原因是严重的胚胎和胚外血管生成缺陷以及心肌小梁形成受损。SGK1 的缺失会导致内皮细胞和血管平滑肌细胞凋亡增加，突出了 SGK1 在血管生成过程中的生存促进作用。Sgk1 缺失的胚胎还表现出 Notch 信号基因表达水平降低和动脉标记物 Efnb2 和 Nrp1 表达降低。这些发现揭示了 SGK1 在心血管发育中的新的和必要的功能，有助于更好地理解哺乳动物的血管生成。
