Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia

Lacko, Lauretta A.; Massimiani, Micol; Sones, Jenny L.; Hurtado, Romulo; Salvi, Silvia; Ferrazzani, Sergio; Davisson, Robin L.; Campagnolo, Luisa; Stuhlmann, Heidi

doi:10.1016/j.mod.2014.04.001

Cited by 32 publications

(28 citation statements)

References 58 publications

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“…Each qRT‐PCR was performed in triplicate with 25 ng cDNA. The relative expression levels of the target genes were calculated and expressed as fold change, 2 – ΔΔ Ct (51).…”

Section: Methodsmentioning

confidence: 99%

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia

et al. 2018

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Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

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“…Each qRT‐PCR was performed in triplicate with 25 ng cDNA. The relative expression levels of the target genes were calculated and expressed as fold change, 2 – ΔΔ Ct (51).…”

Section: Methodsmentioning

confidence: 99%

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia

et al. 2018

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“…The first observations that EGFL7 could control Notch signaling were made in neural stem cell cultures where it was found that the N-terminal half of EGFL7 specifically interacted with EGF domains in Notch1-4 and inhibited Notch signaling [40]. Subsequent work showed that EGFL7 control of Notch in endothelial and placental trophoblast cells was important for placenta development and that decreased EGFL7 expression may be linked to preeclampsia [41, 42]. In addition to controlling Notch via direct interaction with Notch receptors, recent work showed that RGD→RGE mutation of the EGFL7 integrin-binding domain enhanced Notch signaling in endothelial cells [32].…”

Section: Direct Ecm-notch Interactions That Control Notch Signalingmentioning

confidence: 99%

Notch: A multi-functional integrating system of microenvironmental signals

LaFoya

Munroe

Mia

et al. 2016

Developmental Biology

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The Notch signaling cascade is an evolutionarily ancient system that allows cells to interact with their microenvironmental neighbors through direct cell-cell interactions, thereby directing a variety of developmental processes. Recent research is discovering that Notch signaling is also responsive to a broad variety of stimuli beyond cell-cell interactions, including: ECM composition, crosstalk with other signaling systems, shear stress, hypoxia, and hyperglycemia. Given this emerging understanding of Notch responsiveness to microenvironmental conditions, it appears that the classical view of Notch as a mechanism enabling cell-cell interactions, is only a part of a broader function to integrate microenvironmental cues. In this review, we summarize and discuss published data supporting the idea that the full function of Notch signaling is to serve as an integrator of microenvironmental signals thus allowing cells to sense and respond to a multitude of conditions around them.

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“…Placentas lacking transcriptional co-repressor Tle3 , a downstream effector of Notch signaling that is co-expressed with Notch2 in Ch-TGCs, have small, abnormally shaped venous channels [8]. In humans, expression of JAG1 is reduced in invasive TBs from women with preeclampsia [24] and expression of EGFL7, a modulator of NOTCH signaling, is reduced in preeclamptic placentas [25]. …”

Section: Introductionmentioning

confidence: 99%

Dynamic maternal and fetal Notch activity and expression in placentation

et al. 2017

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Introduction Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands. Methods Notch reporter transgenic mice were used to define canonical Notch activity and immunofluorescence staining performed to characterize expression of Notch1, 2, 3, 4 and ligands, Delta-like 4 (Dll4) and Jagged1 (Jag1) during early placentation and in the mature placenta. Results Notch signaling is active in maternal and fetal endothelial cells and trophoblasts during early placentation and in the mature placenta. Dll4, Jag1, Notch1, and Notch4 are expressed in maternal vasculature in the decidua. Dll4, Jag1 and Notch1 are expressed in fetal vasculature in the labyrinth. Dll4, Notch2 and Notch4 are co-expressed in the ectoplacental cone. Notch2 and Notch4 are expressed in parietal-trophoblast giant cells and junctional zone trophoblasts with active canonical Notch signaling and in labyrinthine syncytiotrophoblasts and sinusoidal-trophoblast giant cells. Discussion Canonical Notch activity and distinct expression patterns for Notch proteins and ligands was evident in endothelium and trophoblasts, suggesting Notch1, Notch2, Notch4, Dll4, and Jag1 have distinct and overlapping functions in placentation. Characterization of Notch signaling defects in existing mouse models of preeclampsia may shed light on the role of Notch in developing the preeclampsia phenotype.

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Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia

Cited by 32 publications

References 58 publications

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia

Notch: A multi-functional integrating system of microenvironmental signals

Dynamic maternal and fetal Notch activity and expression in placentation

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