Dataset Information

STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.

ABSTRACT: BACKGROUND: Mutations in STOX1 were proposed to be causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. METHODOLOGY AND PRINCIPAL FINDINGS: In the present study, we have produced a choriocarcinoma cell line overexpressing STOX1. This overexpression results in transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r = 0.30, p = 9.10(-7)). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chorionic gonadotrophin -hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells. CONCLUSIONS: Our results contribute to reconcile contradictory data concerning the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Our cellular model could constitute an invaluable resource for studying specific aspects of this human disease.

SUBMITTER: Rigourd V

PROVIDER: S-EPMC2592700 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.

Rigourd Virginie V Chauvet Caroline C Chelbi Sonia T ST Rebourcet Régis R Mondon Françoise F Letourneur Franck F Mignot Thérèse-Marie TM Barbaux Sandrine S Vaiman Daniel D

PloS one 20081211 12

<h4>Background</h4>Mutations in STOX1 were proposed to be causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation.<h4>Methodology and principal findings</h4>In the present study, we have produced a choriocarcinoma cell line overexpressing STOX1. This overexpressi ...[more]

PMID: 19079545

Similar Datasets

Project description:Hydroxychloroquine (HCQ), an anti-malarial drug, is suggested as a promising candidate for the treatment of pregnancy-related disorders associated with endothelial activation, among which there is preeclampsia (PE). Arterial feto-placental endothelial cells (fpECAs) were isolated from control (CTR) and early-onset preeclamptic (EO-PE) placentas. The aim of this study was to test potential protective effects of HCQ in an in vitro model of endothelial activation as well as in cells isolated from EO-PE placentas. To mimic PE conditions, CTR fpECAs were exposed to a pro-inflammatory environment consisting of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β (furtherly referred as MIX) with or without varying concentrations of HCQ (1 µg/mL and 10 µg/mL). Their effect on wound healing and endothelial barrier integrity was analyzed. Variations in the expression of IL-8 and leukocyte adhesion molecules (LAM) on both mRNA and protein levels were determined between CTR and PE fpECAs in the presence or absence of HCQ. MIX decreased wound healing and stability of the endothelial barrier, but HCQ did not affect it. Significant differences between CTR and EO-PE fpECAs were observed in IL-8 mRNA, protein secretion, and vascular cell adhesion protein 1 (VCAM-1) mRNA expression levels. After challenging CTR fpECAs with MIX, upregulation of both mRNA and protein levels was observed in all molecules. Combined treatment of HCQ and MIX slightly lowered VCAM-1 total protein amount. In CTR fpECAs, treatment with low concentrations of HCQ alone (1 µg/mL) reduced basal levels of IL-8 and VCAM-1 mRNA and secretion of IL-8, while in EO-PE fpECAs, a higher (10µg/mL) HCQ concentration slightly reduced the gene expression of IL-8. Conclusion: These results provide additional support for the safety of HCQ, as it did not adversely affect endothelial functionality in control fpECAs at the tested concentration. Furthermore, the observed limited effects on IL-8 secretion in EO-PE fpECAs warrant further investigation, highlighting the need for clinical trials to assess the potential therapeutic effects of HCQ in preeclampsia. Conducting clinical trials would offer a more comprehensive understanding of HCQ's efficacy and safety, allowing us to explore its potential benefits and limitations in a real-world clinical setting.

Project description:BackgroundAlthough preeclampsia has long been recognized as a condition affecting late pregnancy, little is known of its pathogenesis or treatment. The placenta releases a number of hormones and molecules that influence the course of pregnancy, one of which is chromogranin A, a soluble protein secreted mainly from the chromaffin cells of the adrenal medulla. Its role in pregnancy and pregnancy-related disorders remains unclear. Therefore, the main aim of the proposed study is to determine whether chromogranin A is related with the occurrence of preeclampsia.MethodsPlacental samples were collected from 102 preeclamptic patients and 103 healthy controls, and Chromogranin A gene (CHGA) expression was measured using real-time RT-PCR, The RT-PCR results were verified on the protein level using ELISA. The normal distribution of the data was tested using the Shapiro-Wilk test. The clinical and personal characteristics of the groups were compared using the Student's t-test for normally-distributed data, and the χ2 test for categorical variables. The Mann-Whitney U test was used for non-normally distributed data. As the log- transformation was not suitable for the given outcomes, the Box- Cox Transformation was used to normalize data from ELISA tests and CHGA expression. Values of P < .05 were considered statistically significant.ResultsChromogranin A gene expression was found to be significantly higher in the study group than in controls. Protein analyses showed that although the CgA concentration in placental samples did not differ significantly, the catestatin (CST) level was significantly lower in samples obtained from women with preeclampsia, according to the controls.Conclusions for practiceThis study for the first time reveals that chromogranin A gene expression level is associated with preeclampsia. Moreover, the depletion in catestatin level, which plays a protective role in hypertension development, might be a marker of developing preeclampsia. Further studies may unravel role of Chromogranin A in the discussed disease.

Dataset Information

STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.

Publications

STOX1 overexpression in choriocarcinoma cells mimics transcriptional alterations observed in preeclamptic placentas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets