胚胎着床过程中的前列腺素调控网络

Network Regulation of Prostaglandin Pathway during Embryo Implantation

已证实与前列腺素代谢相关的Cox-2、cPLA_(2α)或Lpar3基因敲除的小鼠都表现为着床延迟,而着床前注射前列腺素可以挽救胚胎着床,表明前列腺素在胚胎着床过程中起重要作用。越来越多的证据表明,前列腺素可以通过cAMP/PKA和PI3K/AKT通路活化β-catenin,又可以通过基质金属蛋白酶(matrix metalloproteinase,MMP)活化肝素结合类表皮生长因子(heparin-binding EGF-likegrowth factor,HB-EGF),还可以通过Src和IL-6活化信号传导与转录激活因子3(signal transducer andactivator of transcription 3,STAT3)。而这些分子活化后又可上调COX-2。此外,前列腺素相关分子内部也存在着正反馈调节。这几个通路之间的相互作用形成了一个网络,在胚胎着床过程中可能发挥重要作用。

Prostaglandin （PG） could rescue delayed implantation deficiencies in Cox-2-, cPLA2a- or Lpar3- deficient mice, respectively, suggesting that prostaglandin was important for implantation. PG could activate β-catenin through cAMP/PKA and PI3K/AKT, activate heparin-binding EGF-like growth factor （HB-EGF） pathway through matrix metalloproteinase cleavage and activate signal transducer and activator of transcription 3 （STAT3） through Src and IL-6. At the same time, COX-2 could be up-regulated by β-catenin, HB-EGF and STAT3. The genes in prostaglandin pathway could also form a positive feedback loop. The interactions among these pathways form a network, which may play important roles during embryo implantation.