The Preeclamptic Environment Promotes the Activation of Transcription Factor Kappa B by P53/RSK1 Complex in a HTR8/SVneo Trophoblastic Cell Line.

Agata Sakowicz,Michalina Bralewska,Lidia Biesiada,Agnieszka Gach,Dominika E Habrowska-Górczyńska,Hubert Huras,Francesc Figueras,Mariusz Grzesiak,Magda Rybak-Krzyszkowska,Agnieszka W Piastowska-Ciesielska,Bartosz Sakowicz,Tadeusz Pietrucha

doi:10.3390/ijms221910200

Abstract

Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NFκB) in maternal and placental cells. Although the role of NFκB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NFκB activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NFκB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NFκB activation. One such pathway depends on the activation of NFκB by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNFκB Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNFκB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53/RSK1 complex might play a critical role in the activation of NFκB in trophoblastic cells and preeclamptic placentas.

Highlights

The success of each pregnancy is determined by a complex set of processes, including trophoblast invasion into maternal decidua, remodeling of maternal spiral arteries, and the adaptation of the maternal immunological system to tolerate the foreign antigens of the developing fetus [1].At the beginning of each pregnancy (
This study investigates the process of nuclear factor kappa B (NFkB) activation in a trophoblastic cell line under stimulation by maternal serum obtained from preeclamptic or normotensive women
Of the tested activity is known to be elevated in preeclampsia, our findings indicate that experimental variants, the highest NFkB level was observed in cells kept in medium with components included inserum maternal may play a role in its development

Summary

Introduction

The success of each pregnancy is determined by a complex set of processes, including trophoblast invasion into maternal decidua, remodeling of maternal spiral arteries, and the adaptation of the maternal immunological system to tolerate the foreign antigens of the developing fetus [1].At the beginning of each pregnancy (1 mg/dL, elevated transaminase levels, thrombocytopenia, haemolysis, neurological disorders or uteroplacental dysfunction (i.a., fetal growth restriction) [7,8]. The etiology of this phenomenon remains a mystery, it is known that both maternal and placental factors play a significant role in its development

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