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Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines

CD24 is a mucin-like immunosuppressing glycoprotein whose levels increase during pregnancy and decrease in the syncytio- and cytotrophoblasts in early and preterm preeclampsia. We used two modified cell lines that mimic in vitro features of preeclampsia to identify if this phenomenon could be reprod...

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Detalles Bibliográficos
Autores principales: Sammar, Marei, Apicella, Clara, Altevogt, Peter, Meiri, Hamutal, Vaiman, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783292/
https://www.ncbi.nlm.nih.gov/pubmed/36555567
http://dx.doi.org/10.3390/ijms232415927
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author Sammar, Marei
Apicella, Clara
Altevogt, Peter
Meiri, Hamutal
Vaiman, Daniel
author_facet Sammar, Marei
Apicella, Clara
Altevogt, Peter
Meiri, Hamutal
Vaiman, Daniel
author_sort Sammar, Marei
collection PubMed
description CD24 is a mucin-like immunosuppressing glycoprotein whose levels increase during pregnancy and decrease in the syncytio- and cytotrophoblasts in early and preterm preeclampsia. We used two modified cell lines that mimic in vitro features of preeclampsia to identify if this phenomenon could be reproduced. Our model was the immortalized placental-derived BeWo and JEG-3 cell lines that overexpress the STOX1 A/B transcription factor gene that was discovered in familial forms of preeclampsia. BeWo and JEG-3 cells stably transduced with the two major isoforms of STOX1-A/B or by an empty vector (control), were propagated, harvested, and analyzed. CD24 mRNA expression was determined by quantitative real-time polymerase nuclear chain reaction (qRT-PCR). CD24 protein levels were determined by Western blots. In STOX1-A/B overexpressing in BeWo cells, CD24 mRNA was downregulated by 91 and 85%, respectively, compared to the control, and by 30% and 74%, respectively in JEG-3 cells. A 67% and 82% decrease in CD24 protein level was determined by immunoblot in BeWo overexpressing STOX1-A/B, respectively, while the reduction in JEG-3 cells was between 47 and 62%. The immortalized BeWo and JEG-3 cell lines overexpressing STOX1-A/B had reduced CD24. Although both cell lines were affected, BeWo appears to be more susceptible to downregulation by STOX-1 than JEG-3, potentially because of their different cell origin and properties. These results strengthen the in vivo results of reduced CD24 levels found in early and preterm preeclampsia. Accordingly, it implies the importance of the reduced immune tolerance in preeclampsia, which was already demonstrated in vivo in the STOX1-A/B model of preeclampsia, and is now implied in the in vitro STOX-1 model, a subject that warrants further investigations.
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spelling pubmed-97832922022-12-24 Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines Sammar, Marei Apicella, Clara Altevogt, Peter Meiri, Hamutal Vaiman, Daniel Int J Mol Sci Communication CD24 is a mucin-like immunosuppressing glycoprotein whose levels increase during pregnancy and decrease in the syncytio- and cytotrophoblasts in early and preterm preeclampsia. We used two modified cell lines that mimic in vitro features of preeclampsia to identify if this phenomenon could be reproduced. Our model was the immortalized placental-derived BeWo and JEG-3 cell lines that overexpress the STOX1 A/B transcription factor gene that was discovered in familial forms of preeclampsia. BeWo and JEG-3 cells stably transduced with the two major isoforms of STOX1-A/B or by an empty vector (control), were propagated, harvested, and analyzed. CD24 mRNA expression was determined by quantitative real-time polymerase nuclear chain reaction (qRT-PCR). CD24 protein levels were determined by Western blots. In STOX1-A/B overexpressing in BeWo cells, CD24 mRNA was downregulated by 91 and 85%, respectively, compared to the control, and by 30% and 74%, respectively in JEG-3 cells. A 67% and 82% decrease in CD24 protein level was determined by immunoblot in BeWo overexpressing STOX1-A/B, respectively, while the reduction in JEG-3 cells was between 47 and 62%. The immortalized BeWo and JEG-3 cell lines overexpressing STOX1-A/B had reduced CD24. Although both cell lines were affected, BeWo appears to be more susceptible to downregulation by STOX-1 than JEG-3, potentially because of their different cell origin and properties. These results strengthen the in vivo results of reduced CD24 levels found in early and preterm preeclampsia. Accordingly, it implies the importance of the reduced immune tolerance in preeclampsia, which was already demonstrated in vivo in the STOX1-A/B model of preeclampsia, and is now implied in the in vitro STOX-1 model, a subject that warrants further investigations. MDPI 2022-12-14 /pmc/articles/PMC9783292/ /pubmed/36555567 http://dx.doi.org/10.3390/ijms232415927 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Sammar, Marei
Apicella, Clara
Altevogt, Peter
Meiri, Hamutal
Vaiman, Daniel
Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title_full Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title_fullStr Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title_full_unstemmed Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title_short Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines
title_sort modeling preeclampsia in vitro: polymorphic variants of stox1-a/b genes can downregulate cd24 in trophoblast cell lines
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783292/
https://www.ncbi.nlm.nih.gov/pubmed/36555567
http://dx.doi.org/10.3390/ijms232415927
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