Castro-Parodi M, Levi L, Dietrich V, Zotta E, Damiano A E
Cátedra de Biología Celular, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires, Junín 956 1er piso, CP 1113 Buenos Aires, Argentina.
Placenta. 2009 Jul;30(7):642-8. doi: 10.1016/j.placenta.2009.04.012. Epub 2009 May 28.
Preeclampsia (PE) is a hypertensive disorder unique to human pregnancy. Although its causes remain unclear, it is known that altered placental villous angiogenesis and a poorly developed fetoplacental vasculature can affect the transport functions of the syncytiotrophoblast (hST). We have previously observed that in preeclamptic placentas there is an increase in AQP9 protein expression, with a lack of functionality. Up to now, the mechanisms for AQP9 regulation and the role of AQP9 in the human placenta remain unknown. However, there is strong evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) regulates AQP9 functionality.
Here, we studied CFTR expression and localization in hST from preeclamptic placentas in order to investigate if alterations in CFTR may be associated with the lack of activity of AQP9 observed in PE.
The expression of CFTR in normal and preeclamptic placentas was determined by Western Blot and immunohistochemistry, and CFTR-AQP9 co-localization was determined by immunoflurescence. Water uptake experiments were performed using explants from human normal term and preeclamptic placentas treated with CFTR inhibitors.
We found that CFTR expression significantly decreased in preeclamptic placentas, and that the hST apical labeling almost disappeared, losing its co-localization with AQP9. Functional experiments demonstrated that water uptake diminished in normal term explants incubated with CFTR inhibitors.
These results suggest that CFTR expression decreases in preeclampsia and may thus be implicated in the regulation of AQP9 activity.
子痫前期（PE）是人类妊娠特有的一种高血压疾病。尽管其病因尚不清楚，但已知胎盘绒毛血管生成改变和胎儿胎盘血管系统发育不良会影响合体滋养层细胞（hST）的转运功能。我们之前观察到，子痫前期胎盘组织中AQP9蛋白表达增加，但缺乏功能。到目前为止，AQP9的调控机制以及AQP9在人胎盘中的作用仍不清楚。然而，有强有力的证据表明囊性纤维化跨膜传导调节因子（CFTR）调节AQP9的功能。
在此，我们研究了CFTR在子痫前期胎盘组织hST中的表达和定位，以探讨CFTR的改变是否可能与子痫前期中观察到的AQP9活性缺乏有关。
通过蛋白质免疫印迹法和免疫组织化学法测定正常胎盘和子痫前期胎盘组织中CFTR的表达，并通过免疫荧光法测定CFTR与AQP9的共定位。使用来自正常足月和子痫前期胎盘组织的外植体，用CFTR抑制剂处理后进行水摄取实验。
我们发现子痫前期胎盘组织中CFTR表达显著降低，hST顶端标记几乎消失，失去了与AQP9的共定位。功能实验表明，用CFTR抑制剂孵育的正常足月外植体中水摄取减少。
这些结果表明，子痫前期中CFTR表达降低，因此可能参与了AQP9活性的调节。
