Expression profiles and functions of ferroptosis-related genes in the placental tissue samples of early- and late-onset preeclampsia patients

Yang, Nana; Wang, Qiang-Hua; Ding, Biao; Gong, Yingying; Wu, Yue; Sun, Junpei; Wang, Xuegu; Liu, Lei; Zhang, Feng; Du, Daolin; Li, Xiang

doi:10.1186/s12884-022-04423-6

Cited by 18 publications

(14 citation statements)

References 56 publications

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“…Previous studies have shown that preeclampsia was considered to be associated with high iron status and ferroptosis. Placenta [28,29] and different cell lineages at the maternal-fetal interface, [30] including trophoblasts, dendritic cells, stromal fibroblasts, and decidual cells are proved to have different modes of intracellular iron regulation and distinctive sensitivities to ferroptosis. However, many ferroptosis genes have yet to be characterized, and ferroptosis-related genes in STB-EVs are not explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Xiang

et al. 2022

Medicine

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Preeclampsia (PE), defined as new-onset hypertension and multi-organ systemic complication during pregnancy, is the leading cause of maternal and neonatal mortality and morbidity. With extracellular vesicles research progresses, current data refers to the possibility that ferroptosis may play a role in exosomal effects. Evidence has suggested that ferroptosis may contribute to the pathogenesis of preeclampsia by bioinformatics analyses. The purpose of the current study is to identify the potential ferroptosisrelated genes in syncytiotrophoblast-derived extracellular vesicles (STB-EVs) of preeclampsia using bioinformatics analyses. Clinical characteristics and gene expression data of all samples were obtained from the NCBI GEO database. The differentially expressed mRNAs (DE-mRNAs) in STB-EVs of preeclampsia were screened and then were intersected with ferroptosis genes. Functional and pathway enrichment analyses of ferroptosis-related DE-mRNAs in STB-EVs were performed. Ferroptosis-related hub genes in STB-EVs were identified by Cytoscape plugin CytoHubba with a Degree algorithm using a protein-protein interaction network built constructed from the STRING database. The predictive performance of ferroptosis-related hub genes was determined by a univariate analysis of receiver operating characteristic (ROC). The miRNA-hub gene regulatory network was constructed using the miRwalk database. A total of 1976 DE-mRNAs in STB-EVs were identified and the most enriched item identified by gene set enrichment analysis was signaling by G Protein-Coupled Receptors (normalized enrichment score = 1.238). These DE-mRNAs obtained 26 ferroptosis-related DE-mRNAs. Ferroptosis-related DE-mRNAs of gene ontology terms and Encyclopedia of Genes and Genomes pathway enrichment analysis were enriched significantly in response to oxidative stress and ferroptosis. Five hub genes (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) were found in the constructed protein-protein interaction network with ferroptosis-related DE-mRNAs and the areas under the ROC curves for ALB, NOX4, CDKN2A, TXNRD1, and CAV1 were 0.938 (CI: 0.815−1.000), 0.833 (CI: 0.612−1.000), 0.875 (CI: 0.704−1.000), 0.958 (CI: 0.862−1.000), and 0.854 (CI: 0.652−1.000) in univariate analysis of ROC. We constructed a regulatory network of miRNA-hub gene and the findings demonstrate that hsa-miR-26b-5p, hsa-miR-192-5p, hsa-miR-124-3p, hsa-miR-492, hsa-miR-34a-5p and hsa-miR-155-5p could regulate most hub genes. In this study, we identified several central genes closely related to ferroptosis in STB-EVs (ALB, NOX4, CDKN2A, TXNRD1, and CAV1) that are potential biomarkers related to ferroptosis in preeclampsia. Our findings will provide evidence for the involvement of ferroptosis in preeclampsia and improve the understanding of ferroptosis-related molecular pathways in the pathogenesis of preeclampsia.Abbreviations: ALB = albumin, CAV1 = caveolin 1, CDKN2A = cyclin dependent kinase inhibitor 2A, DEGs = differentially expressed genes, DE-mRNAs = differentially expressed mRNAs, EVs = extracellular v...

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Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Xiang

et al. 2022

Medicine

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“…It has also been found that miR-30b-5p in PE models can reduce the expression of ferroportin 1 by downregulating Cys2/glutamate antiporter and PAX3, leading to a decrease in GSH and an increase in labile Fe 2+ , therefore promoting the occurrence of ferroptosis in PE patients [ 126 ]. The expression of miR-210 was also found to be increased in placenta in PE models, resulting in iron accumulation and autophagosome formation in trophoblast cells and hemosiderin deposition in placental stroma trophoblasts [ 127 ]. Genetic studies have also found that, in PE, the expression levels of genes mainly responsible for iron metabolism ( FTH1 and FTL ) are downregulated, leading to disruption of iron uptake and intracellular storage, thereby promoting cellular ferroptosis [ 128 ].…”

Section: Ferroptosis and Pre-eclampsiamentioning

confidence: 99%

Ferroptosis and Its Emerging Role in Pre-Eclampsia

et al. 2022

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Iron is essential for cell survival, and iron deficiency is a known risk factor for many reproductive diseases. Paradoxically, such disorders are also more common in cases of iron overload. Here, we evaluated the role of ferroptosis in women’s health, particularly focusing on pre-eclampsia (PE). PE is a multisystem disorder and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Nevertheless, the exact etiological mechanism of PE remains unclear. Interestingly, ferroptosis, as a regulated iron-dependent cell death pathway, involves a lethal accumulation of lipid peroxides and shares some characteristics with PE pathophysiology. In this review, we comprehensively reviewed and summarized recent studies investigating the molecular mechanisms involved in the regulation and execution of ferroptosis, as well as ferroptosis mechanisms in the pathology of PE. We propose that ferroptosis not only plays an important role in PE, but may also become a novel therapeutic target for PE.

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“…Preeclampsia is associated with insufficient trophoblast infiltration and impaired vascular remodeling in spiral arteries [64]. Impaired vascular remodeling in preeclampsia reduces placental perfusion and oxygenation, and increases oxidative stress with ROS and toxic lipid peroxides [65]. Free radicals activate monocytes and neutrophils to produce pro-inflammatory cytokines, and further produce ROS through the action of various enzymes and the large amount of ROS produced by oxidative stress can damage the trophoblast cell mitochondrial membrane, permeable transport pore, mitochondrial DNA, and mitochondrial enzymes, which in turn triggers preeclampsia, premature rupture of membrane, etc.…”

Section: Abnormal Placental Vascular Remodelingmentioning

confidence: 99%

An Update Review of the Pathogenesis Hypothesis in Preeclampsia

Li¹,

Zhu²,

Xi³

2022

Clin. Exp. Obstet. Gynecol.

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Objectives: Hypertensive disorders occur in approximately 12% to 22% of pregnancies and cause substantial perinatal morbidity and mortality of both mother and fetus. Hypertensive disease is directly responsible for approximately 20% of maternal deaths and can be classified as chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and chronic hypertension with superimposed preeclampsia. At present, the pathogenesis of preeclampsia is still unclear, we wrote this article to make a uptodate review of this disease. Mechanism: A comprehensive search of several databases was conducted from inception up to March 2022. The searched databases were Web of Science, MEDLINE,Ovid, and Cochrane Database of Systematic Reviews. The search strategy included the combinations of the following medical terms: Hypertensive disorders; preeclampsia; mechanism; pathogenesis hypothesis. Findings in Brief: At present,the pathogenesis of preeclampsia is still unclear, the theory of Genetic,Inflammatory Response, Immune Imbalance in Maternal-Fetal Interface, Oxidative Stress, Vascular Endothelial Cell Damage are supposed involved in the progress of preeclampsia. Conclusions: Although there are various theories mentioned above, none of the hypothesis can fully explain preeclampsia. More research is needed on the mechanism of preeclampsia.

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Expression profiles and functions of ferroptosis-related genes in the placental tissue samples of early- and late-onset preeclampsia patients

Cited by 18 publications

References 56 publications

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Identification of ferroptosis-related genes in syncytiotrophoblast-derived extracellular vesicles of preeclampsia

Ferroptosis and Its Emerging Role in Pre-Eclampsia

An Update Review of the Pathogenesis Hypothesis in Preeclampsia

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