MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
Mol Hum Reprod. 2010 May;16(5):311-9. doi: 10.1093/molehr/gaq014. Epub 2010 Feb 19.
The onset of labour is associated with inflammatory cascades in the uteroplacental unit, and these are prematurely activated in preterm labour. Infection can induce an inflammatory response, which results in premature onset of the pro-inflammatory parturient cascades and preterm delivery. We have become interested in two proteins called prokineticins and the role they may play in labour and its premature onset. Prokineticin 1 and 2 bind to two G-protein coupled receptors, called prokineticin receptor 1 and 2. Expression of the prokineticins and their receptors is elevated in the uteroplacental unit during labour and they can induce expression of a host of genes known to be important in initiating the inflammatory and contractile events of labour. Prokineticins have also been shown to directly induce contractility of smooth muscles. Analysing the promoter regions of the prokineticins and their receptors highlights their potential regulation by pathways activated by infectious agents. Hence, we propose that infection can result in premature activation of prokineticin expression and signalling in the uteroplacental unit and this initiates a premature inflammatory and contractile cascade leading to preterm birth. Antagonism of prokineticin action may provide a suitable therapy for preterm labour that targets both inflammation and contractile pathways.
分娩的开始与胎盘单位中的炎症级联反应有关，而这些在早产中会过早激活。感染会引发炎症反应，导致促炎分娩级联的过早发生和早产。我们对两种称为促动力蛋白的蛋白质产生了兴趣，以及它们在分娩及其过早开始中可能发挥的作用。促动力蛋白 1 和 2 与两种 G 蛋白偶联受体结合，称为促动力蛋白受体 1 和 2。在分娩期间，促动力蛋白及其受体在胎盘单位中的表达增加，它们可以诱导已知在引发炎症和收缩性分娩事件中重要的一系列基因的表达。促动力蛋白也被证明可以直接诱导平滑肌的收缩性。分析促动力蛋白及其受体的启动子区域突出了它们可能受到感染剂激活的途径的调节。因此，我们提出感染会导致胎盘单位中促动力蛋白表达和信号的过早激活，从而引发早产的炎症和收缩性级联反应。拮抗促动力蛋白的作用可能为治疗早产提供一种合适的治疗方法，该方法既针对炎症途径，也针对收缩性途径。
