Molecular mechanisms of ductus arteriosus closure

动脉导管（ductus arteriosus，DA）是胎儿的重要动脉，出生后立即关闭。然而，其分子机制仍不清楚，尤其是血管重塑。我们发现：1）前列腺素E2（PGE 2）-EP 4信号通过降解交联酶赖氨酰氧化酶而减少弹性纤维的形成; 2）NFkB信号可以通过cAMP非依赖性途径被PGE 2-EP 4刺激激活; 3）DA的内皮细胞表现出参与DA特异性形态和功能调节的独特基因谱。这些关于DA血管重塑的新发现可能为创新调节DA闭合的新治疗策略开辟了可能性。

The ductus arteriosus (DA) is an essential fetal artery that closes immediately after birth. However, the molecular mechanisms remain unknown, especially its vascular remodeling. We found that 1) prostaglandin E2 (PGE2) -EP4 signaling decreased elastic fiber formation through degradation of the cross-linking enzyme lysyl oxidase, and that 2) NFkB signal could be activated by PGE2-EP4 stimulation via cAMP-independent pathway, and that 3) endothelial cells of the DA exhibited a unique gene profile involved in the regulation of DA-specific morphology and function. These novel findings regarding DA vascular remodeling could open a possibility to innovate a new therapeutic strategy for the regulation of DA closure.