Modelling preeclampsia: a comparative analysis of the common human trophoblast cell lines

Zhao, Jiawu; Chow, Rebecca P.; McLeese, Rebecca H.; Hookham, Michelle B.; Lyons, Timothy; Yu, Yongxin

doi:10.1096/fba.2020-00057

Cited by 10 publications

(7 citation statements)

References 78 publications

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“…Additionally, no data exist regarding the role of the CgA-derived peptide CST in pregnancy or PE, nor of its presence in the cell cultures representing human trophoblast. Although various studies on, inter alia, apoptosis, hypoxia and oxidative stress have been performed on trophoblastic cell lines, none have examined whether those cells are able to produce CgA and secrete CST [ 4 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment

Bralewska

Pietrucha

Sakowicz

2023

IJMS

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One of the most dangerous complications of pregnancy is preeclampsia (PE), a disease associated with a high risk of maternal and fetal mortality and morbidity. Although its etiology remains unknown, the placenta is believed to be at the center of ongoing changes. One of the hormones produced by the placenta is chromogranin A (CgA). Thus far, its role in pregnancy and pregnancy-related disorders is enigmatic, yet it is known that both CgA and its derived peptide catestatin (CST) are involved in the majority of the processes that are disturbed in PE, such as blood pressure regulation or apoptosis. Therefore, in this study, the influence of the preeclamptic environment on the production of CgA using two cell lines, HTR-8/SVneo and BeWo, was investigated. Furthermore, the capacity of trophoblastic cells to secrete CST to the environment was tested, as well as the correlation between CST and apoptosis. This study provided the first evidence that CgA and CST proteins are produced by trophoblastic cell lines and that the PE environment has an impact on CST protein production. Furthermore, a strong negative correlation between CST protein level and apoptosis induction was found. Hence, both CgA and its derived peptide CST may play roles in the complex process of PE pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment

Bralewska

Pietrucha

Sakowicz

2023

IJMS

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“…As shown in Figure 3A, hypoxia treatment (1% oxygen for 24 h) increased supernatant sFlt1 protein concentrations in BeWo cells by approximately 2-fold vs. normoxia (50.0 ± 3.1 pg/mL vs. 26.3 ± 3.6 pg/mL, respectively). This effect was blocked by 10 nmol/L of the HIFα inhibitor chetomin [31]. We found that neither aspirin (10 and 50 µmol/L) nor salicylic acid (20 and 100 µmol/L) had any significant effect on sFlt1 protein release (Figure 3B,D) or mRNA expression (Figure 3C,E).…”

Section: Effects Of Aspirin and Salicylic Acid On Hypoxia-induced Sfl...mentioning

confidence: 82%

“…Salicylic acid at 100 µmol/L appeared to cause a non-significant increase of sFlt1 mRNA expression, but not at the protein level. Since we previously found that sFlt1 protein release and mRNA expression were not stimulated by hypoxia in this cell line [31], we did not test drug effects under this condition.…”

Section: Effects Of Aspirin and Salicylic Acid On Sflt1 Protein Relea...mentioning

confidence: 99%

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An Examination of the Effect of Aspirin and Salicylic Acid on Soluble Fms-like Tyrosine Kinase-1 Release from Human Placental Trophoblasts

Zhao,

Duan,

Sun

et al. 2024

Cells

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Low-dose aspirin (LDA) is efficacious in preventing preeclampsia, but its mechanism of action is unclear. Conflicting evidence suggests that it may inhibit placental trophoblast release of soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. We examined whether, and at what concentrations, aspirin and its principal metabolite, salicylic acid, modulate sFlt1 release and/or expression in trophoblasts. Human trophoblast lines BeWo and HTR-8/SVneo were cultured; BeWo cells were also treated with 1% oxygen vs. normoxia to mimic hypoxia in preeclamptic placentas. Cells were treated with aspirin or salicylic acid vs. vehicle for 24 h at concentrations relevant to LDA and at higher concentrations. Protein concentrations (ELISA) and mRNA expression (RT-PCR) of sFlt1 were determined. Under normoxia, LDA-relevant concentrations of aspirin (10–50 µmol/L) or salicylic acid (20–100 µmol/L) had no significant effect on sFlt1 protein release or mRNA expression in BeWo cells. However, inhibition was observed at higher concentrations (1 mmol/L for aspirin and ≥200 μmol/L for salicylic acid). Hypoxia enhanced sFlt1 protein release and mRNA expression in BeWo cells, but these responses were not significantly affected by either aspirin or salicylic acid at LDA concentrations. Similarly, neither drug altered sFlt1 protein secretion or mRNA expression in normoxic HTR-8/SVneo cells at LDA concentrations. We suggest that direct modulation of trophoblast release or expression of sFlt1 is unlikely to be a mechanism underlying the clinical efficacy of LDA in preeclampsia.

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“…Hypoxia-induced changes in JEG-3 cells involve reduction of the major placental hormone human chorionic gonadotropin (hCG), upregulation of the vascular endothelial growth factor (VEGF) [8] , [10] , and transcriptional regulation of a number of other genes by Hypoxia Inducible Factors (HIFs) [16] . However, results vary depending on the applied hypoxia system [17] , [18] , [19] , [20] , [21] .…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Profiling of JEG-3 cells using human leiomyoma derived matrix

Barmaki

Al‐Samadi

Leskinen

et al. 2022

Biomaterials and Biosystems

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Modelling preeclampsia: a comparative analysis of the common human trophoblast cell lines

Abstract: This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 10 publications

References 78 publications

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment

An Examination of the Effect of Aspirin and Salicylic Acid on Soluble Fms-like Tyrosine Kinase-1 Release from Human Placental Trophoblasts

Transcriptomic Profiling of JEG-3 cells using human leiomyoma derived matrix

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