Die CCN-Proteine CYR61 (CCN1) und NOV (CCN3): Regulatoren der Trophoblastinvasion

子痫前期是一种危及母婴生命的胎盘疾病。对于先兆子痫的发展，最受欢迎的理论是滋养细胞浅层侵入母体间室，包括螺旋动脉，进而影响氧气供应，从而影响胎盘和胚胎的发育。鉴于血管生成和迁移因子CyR61(CCN1)和Nov(CCN3)似乎在调节滋养层细胞的迁移特性中起重要作用，我们希望通过不同的体外模型来研究这两种CCN蛋白的调节和迁移能力。我们将通过以下目的来解决这些问题：(I)将使用绒毛外植体模型(VE)研究绒毛外植体模型(VE)中CyR61和NOV的转录和蛋白表达水平对环境低氧的依赖；(Ii)将使用Matrigel覆盖的跨井室和蜕膜组织共培养来分析CyR61和Nov的表达水平对VE侵袭特性的影响。此外，(Iii)我们将使用转染人绒毛膜癌细胞作为额外的模型系统来研究这两种CCN蛋白对滋养层侵袭特性的贡献。

Preeclampsia is a placental disease which is life-threatening for mother and child. The most favoured theory for the development of preeclampsia is a shallow invasion of the trophoblast into the maternal compartment including spiral arteries which in turn affects oxygen supply and thus placental and embryonic development. Since the angiogenic and migration factors CYR61 (CCN1) and NOV (CCN3) seem to be important players in mediating migration properties of trophoblast cells we would like to investigate regulation of both CCN proteins as well as migration capacities using different in vitro models. We will address these questions by the following aims: (i) the transcript and protein expression levels of CYR61 and NOV in the extravillous trophoblast will be investigated dependent on environmental hypoxia using the extravillous explant model (VE) and (ii) the effect of CYR61 and NOV expression levels on invasion properties of VE will be analysed using matrigel covered transwell chambers and decidual tissue co-cultures. Furthermore (iii) we will utilize human choriocarcinoma cells transfected with CYR61 and/or NOV as an additional model system to investigate the contributions of both CCN proteins for trophoblast invasion properties.