Altered mRNA Expression Pattern of Placental Epidermal Growth Factor Receptor (EGFR) in Pregnancies Complicated by Preeclampsia and/or Intrauterine Growth Retardation

Faxén, Margareta; Nasiell, Josefine; Blanck, Agneta; Nisell, Henry; Lunell, Nils‐Olov

doi:10.1055/s-2007-993890

Cited by 39 publications

(24 citation statements)

References 8 publications

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“…There are other truncated isoforms of the EGFR produced by alternate mRNA splicing or proteolytic cleavage of the full-length receptor [32]. Evaluation of EGFR mRNA expression in PE placentas revealed significantly higher levels of the truncated transcript [19]. Consistent with those findings, we found an increase in p110/EGFR in placentas of PE patients, compared to SGA and PTL patients.…”

Section: Discussionsupporting

confidence: 87%

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Reduced expression of the epidermal growth factor signaling system in preeclampsia

et al. 2015

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Introduction The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries. Methods Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunocytochemistry in the trophoblast of placentas (N=76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides. Results Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p<0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p<0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p< 0.05). Discussion Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia.

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Section: Discussionsupporting

confidence: 87%

“…A truncated EGFR/ERBB1 isoform (p110/EGFR) has been identified and is elevated in PE patients [19]. Because p110/EGFR lacks the cytoplasmic domain, it could act as a dominant negative, adding to the complexity of this biochemical network.…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of the epidermal growth factor signaling system in preeclampsia

et al. 2015

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“…87 EGFR mRNA expression is significantly lower in FGR placentae than that of healthy controls; but in FGR and PE placentae, there is significantly increased expression of the truncated form of EGFR. 88 Furthermore, maternal EGF deficiency causes fetal hypoglycaemia and FGR in mice. 89 Together these data suggest an important role for EGF and EGFR in the regulation of placental development and fetal growth.…”

Section: Altered Expression Of Emt Inducers Transcription Factors Anmentioning

confidence: 99%

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Davies

Pollheimer

Yong

et al. 2016

Cell Adhesion & Migration

216

146

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A successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

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“…However, the analysis of EGFR mRNA expression in the placenta has revealed two different full-length transcripts and one truncated transcript, p110/EGFR. In the preeclamptic placenta two independent studies have found significantly higher mRNA expression of the truncated transcript, while there were no significant differences in the mRNA expression of the two full-length transcripts [43, 45]. Since the p110/EGFR isoform contains an extracellular domain and lacks the intracellular domain it should not be able to signal upon EGF-binding and thus could act as a dominant negative.…”

Section: Discussionmentioning

confidence: 99%

An Integrative Analysis of Preeclampsia Based on the Construction of an Extended Composite Network Featuring Protein-Protein Physical Interactions and Transcriptional Relationships

Vaiman

Miralles

2016

PLoS ONE

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Preeclampsia (PE) is a pregnancy disorder defined by hypertension and proteinuria. This disease remains a major cause of maternal and fetal morbidity and mortality. Defective placentation is generally described as being at the root of the disease. The characterization of the transcriptome signature of the preeclamptic placenta has allowed to identify differentially expressed genes (DEGs). However, we still lack a detailed knowledge on how these DEGs impact the function of the placenta. The tools of network biology offer a methodology to explore complex diseases at a systems level. In this study we performed a cross-platform meta-analysis of seven publically available gene expression datasets comparing non-pathological and preeclamptic placentas. Using the rank product algorithm we identified a total of 369 DEGs consistently modified in PE. The DEGs were used as seeds to build both an extended physical protein-protein interactions network and a transcription factors regulatory network. Topological and clustering analysis was conducted to analyze the connectivity properties of the networks. Finally both networks were merged into a composite network which presents an integrated view of the regulatory pathways involved in preeclampsia and the crosstalk between them. This network is a useful tool to explore the relationship between the DEGs and enable hypothesis generation for functional experimentation.

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Altered mRNA Expression Pattern of Placental Epidermal Growth Factor Receptor (EGFR) in Pregnancies Complicated by Preeclampsia and/or Intrauterine Growth Retardation

Cited by 39 publications

References 8 publications

Reduced expression of the epidermal growth factor signaling system in preeclampsia

Reduced expression of the epidermal growth factor signaling system in preeclampsia

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

An Integrative Analysis of Preeclampsia Based on the Construction of an Extended Composite Network Featuring Protein-Protein Physical Interactions and Transcriptional Relationships

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