Role of lung epithelial Akt signaling in respiratory distress syndrome

AKT是一种丝氨酸/苏氨酸蛋白激酶，被胰岛素激活，调节包括细胞生长和葡萄糖代谢在内的多种细胞过程。肺上皮细胞Akt的过度表达导致肺毛细血管密度降低，HIF-2和VEGF表达下调，导致剖宫产早产儿RDS。雷帕霉素治疗可恢复转基因小鼠肺组织中血管内皮生长因子和缺氧诱导因子-2的表达，改善肺组织病理改变。这些结果提示，肺上皮细胞Akt/mTOR通路的异常激活在RDS的发病机制中起重要作用。

Akt is a serine/threonine protein kinase that is activated by insulin and regulates multiple cellular processes including cell growth and glucose metabolism. Overexpression of Akt in lung epithelium resulted in reduced capillary density and downregulation of HIF-2 and VEGF, leading to RDS in preterm infants born by Caesarean section. Treatment with rapamycin restored the expression of VEGF and HIF-2 and improved the lung pathology of transgenic mice. These results suggest that aberrant activation of Akt/mTOR pathway in the lung epithelium plays a critical role in the pathogenesis of RDS.