Placental Expression of NEMO Protein in Normal Pregnancy and Preeclampsia

正常妊娠和先兆子痫中 NEMO 蛋白的胎盘表达

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作者:Agata Sakowicz, Michalina Lisowska, Lidia Biesiada, Elżbieta Płuciennik, Agnieszka Gach, Magda Rybak-Krzyszkowska, Hubert Huras, Bartosz Sakowicz, Hanna Romanowicz, Agnieszka W Piastowska-Ciesielska, Mariusz Grzesiak, Tadeusz Pietrucha

Background

Preeclamptic pregnancies often present an intensified inflammatory state associated with the nuclear activity of NFκB. NEMO is an essential regulator of nuclear factor kappa B (NFκB) in cytoplasmic and nuclear cellular compartments. The

Conclusions

The depletion of the NEMO protein in the cellular compartments of placental samples may activate one of the molecular pathways influencing the development of preeclampsia, especially in pregnancies with a female fetus. A reduction of the NEMO protein in the nuclear fraction of preeclamptic placentas may intensify the inflammatory state characteristic for preeclampsia and increase the level of apoptosis and necrosis within preeclamptic placentas.

Methods

The study includes 97 preeclamptic cases and 88 controls. NEMO distribution was analyzed immunohistochemically. Its localization in the nuclear and cytoplasmic fractions, as well as in total homogenates of placental samples, was studied by western blot and ELISA.

Results

The western blot and ELISA results indicate a significant difference in NEMO concentration in the total and nuclear fractions between preeclamptic and control samples (p < 0.01 and p < 0.001, respectively). In the cytoplasmic complement, similar levels of NEMO were found in preeclamptic and control placentas. In addition, immunohistochemical staining revealed that the NEMO protein is mainly localized in the syncytiotrophoblast layer, with controls demonstrating a stronger reaction with NEMO antibodies. This study also shows that the placental level of NEMO depends on the sex of the fetus. Conclusions: The depletion of the NEMO protein in the cellular compartments of placental samples may activate one of the molecular pathways influencing the development of preeclampsia, especially in pregnancies with a female fetus. A reduction of the NEMO protein in the nuclear fraction of preeclamptic placentas may intensify the inflammatory state characteristic for preeclampsia and increase the level of apoptosis and necrosis within preeclamptic placentas.

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