Finding NEMO in preeclampsia

Agata Sakowicz, Paulina Hejduk, Tadeusz Pietrucha, Magdalena Nowakowska, Elżbieta Płuciennik, Karolina Pospiech, Agnieszka Gach, Magda Rybak-Krzyszkowska, Bartosz Sakowicz, Marek Kaminski, Grzegorz Krasomski, Lidia Biesiada

The mechanism of preeclampsia and its way of inheritance is still a mystery. Biochemical and immunochemical studies reveal a substantial increase in TNF alpha, IL-1 beta and IL-6 concentrations in blood of preeclamptic women. The level of these factors is regulated by NFĸB, whose activation in a classical pathway requires IKKγ (known as NEMO or IKBKG). Moreover, NEMO can schedule between cytoplasma and nucleus. In nucleus, IKBKG interacts with other proteins and, thus, it is implicated in the regulation of different gene expression which are related to cell cycle progression, proliferation, differentiation and apoptosis. This is the first study investigating the association between the level of NEMO gene expression and the presence of preeclampsia. We tested the hypothesis that the simultaneous increase in NEMO gene expression both in mother and her fetus may be responsible for the preeclampsia development. Moreover, the relationships between clinical risk factors of preeclampsia and levels of NEMO gene expression in blood, umbilical cord blood and placentas were investigated. A total of 91 women (43 preeclamptic women and 48 controls) and their children were examined. Real-time RT-PCR was used to assess the amount total NEMO mRNA content and the mRNA level of each NEMO transcript from exons 1A, 1B and 1C in maternal blood, umbilical cord blood and placentas. Univariate analyses and correlation tests were performed to examine the association between NEMO gene expression and preeclampsia. Newborn weight and height, maternal platelets number and gestational age (week of delivery) were lower in the group of preeclamptic women than controls. NEMO gene expression level was found to be almost 7 times higher in the group of preeclamptic women than healthy controls. The correlation analysis found that a simultaneous increase in the expression level of Total NEMO mRNA in maternal blood and the mRNA for Total NEMO (Rs=0.311 p<0.05), transcripts 1A (Rs=0.463 p<0.01), 1B (Rs=0.454 p<0.01), 1C (Rs=0.563 p<0.001) in fetal blood was observed in preeclamptic pregnancies. In addition, the mRNA levels for Total NEMO and transcripts 1A, 1B and 1C were lower in placentas derived from pregnancies complicated by preeclampsia. Simultaneous increase of NEMO gene expression in maternal and fetal blood seems to be relevant for preeclampsia development. The results of our study also suggest that decreased NEMO gene expression level in preeclamptic placentas may be the main reason for their intensified apoptosis.