RITA Is Expressed in Trophoblastic Cells and Is Involved in Differentiation Processes of the Placenta.

Julia Maria Wildner,Alexandra Friemel,Nina-Naomi Kreis,Juping Yuan,Qi Chen,Cornelia Schüttler,Susanne Roth,Frank Louwen,Lukas Jennewein,Andreas Ritter

doi:10.3390/cells8121484

Julia Maria Wildner, Alexandra Friemel + Show 8 more

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https://doi.org/10.3390/cells8121484

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Journal: Cells	Publication Date: Nov 21, 2019
Citations: 3	License type: CC BY 4.0

Affiliation: Goethe University Frankfurt, University of Auckland

Abstract

Preeclampsia (PE) remains a leading cause of maternal and perinatal mortality and morbidity worldwide. Its pathogenesis has not been fully elucidated and no causal therapy is currently available. It is of clinical relevance to decipher novel molecular biomarkers. RITA (RBP-J (recombination signal binding protein J)-interacting and tubulin-associated protein) has been identified as a negative modulator of the Notch pathway and as a microtubule-associated protein important for cell migration and invasion. In the present work, we have systematically studied RITA’s expression in primary placental tissues from patients with early- and late-onset PE as well as in various trophoblastic cell lines. RITA is expressed in primary placental tissues throughout gestation, especially in proliferative villous cytotrophoblasts, in the terminally differentiated syncytiotrophoblast, and in migrating extravillous trophoblasts. RITA’s messenger RNA (mRNA) level is decreased in primary tissue samples from early-onset PE patients. The deficiency of RITA impairs the motility and invasion capacity of trophoblastic cell lines, and compromises the fusion ability of trophoblast-derived choriocarcinoma cells. These data suggest that RITA may play important roles in the development of the placenta and possibly in the pathogenesis of PE.

Highlights

Preeclampsia (PE) is a pregnancy-specific multi-system hypertensive disorder with a global prevalence of up to 8%, characterized by the de novo onset of concurrent hypertension and proteinuria after 20 weeks of gestation
Protein expression of RITA was analyzed in placental tissues of first trimester, early-onset controls and late-onset controls using immunohistochemistry (IHC)
No staining signal was observed in placental tissue stained with RITA antibody neutralized with its corresponding peptide, evidencing that the RITA signal is specific

Summary

Introduction

Preeclampsia (PE) is a pregnancy-specific multi-system hypertensive disorder with a global prevalence of up to 8%, characterized by the de novo onset of concurrent hypertension and proteinuria after 20 weeks of gestation. Early-onset PE mainly originates from the placenta, and is referred to as placental PE It is tightly associated with defective trophoblast invasion and spiral artery remodeling, while late-onset PE is rather associated with preexisting maternal risk factors like obesity, diabetes, hypertension, or renal disease [5,6]. These classifications have prognostic importance, since placental/early-onset PE entails a greater risk of maternal and fetal complications [7].

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