Localization of Endoglin, a Transforming Growth Factor-β Binding Protein, and of CD44 and Integrins in Placenta during the First Trimester of Pregnancy1

St‐Jacques, Sylvie; Forte, Milena; Lye, Stephen J.; Letarte, Michelle

doi:10.1095/biolreprod51.3.405

Cited by 109 publications

(51 citation statements)

References 38 publications

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“…Endoglin (Eng) is an angiogenic receptor expressed mainly on the surface of endothelial cells, but also placental syncytiotrophoblasts (Cheifetz et al, 1992;Gougos et al, 1992;St-Jacques et al, 1994). Eng acts as a co-receptor for transforming growth factor-beta (TGF-beta), a potent pro-angiogenic molecule, signaling in endothelial cells.…”

Section: Angiogenic Factors In the Pathogenesis Of Preeclampsiamentioning

confidence: 99%

Angiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia

Kopcow

Karumanchi

2007

Journal of Reproductive Immunology

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Preeclampsia is a pregnancy-specific complex disease in which numerous genetic, immunological and environmental factors interact. Characterized by new onset hypertension, proteinuria and edema after 20 weeks of gestation, preeclampsia is often complicated by small-for-gestational-age (SGA) babies and preterm delivery, and is therefore a significant cause of maternal and fetal morbidity and mortality. The only definitive treatment of preeclampsia is delivery of the placenta. Recent data suggest that the anti-angiogenic state induced by excess circulating anti-angiogenic factors of placental origin may be responsible for the clinical signs and symptoms of preeclampsia. Natural killer (NK) cells at the maternal/fetal interface, which are thought to play an important role in normal placental development, have been noted recently to induce angiogenic factors and vascular remodeling. Moreover, genetic studies suggest that susceptibility to preeclampsia may be influenced by polymorphic HLA-C ligands and killer cell receptors (KIR) present on NK cells. This review summarizes our current understanding of the role of angiogenic factors and NK cells in the pathogenesis of preeclampsia.

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Section: Angiogenic Factors In the Pathogenesis Of Preeclampsiamentioning

confidence: 99%

Angiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia

Kopcow

Karumanchi

2007

Journal of Reproductive Immunology

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“…Recently, it has been proposed that serial determinations of the concentrations of sVEGFR-1 [38,39], PlGF [38], and s-Eng [39] are more informative in assessing the risk for PE than are single measurements in the first or second trimester. This is plausible because PlGF, s-Eng, and sVEGFR-1 are produced by the trophoblast [23,[39][40][41][42][43][44] and, therefore, maternal plasma concentrations can change with placental development from the first to the second trimester.…”

mentioning

confidence: 99%

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Erez

Romero

Espinoza

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

269

233

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The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, The Journal of Maternal-Fetal & Neonatal Medicine, 21:5, 279-287, DOI: 10.1080 AbstractIntroduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n ¼ 201); (2) patients who delivered an SGA neonate (n ¼ 145); and (3) patients who developed PE (n ¼ 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results.(1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively).(2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4....

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“…In human, it is expressed at high levels on vascular endothelial cells and on syncytiotrophoblast of term placenta (28 -30). It is transiently expressed on extravillous cytotrophoblasts and induced upon activation of peripheral blood monocytes (31,32). Transient expression of endoglin is also striking during human heart development, as it is expressed at high levels on endocardial cushion tissue mesenchyme during heart septation and valve formation, and subsequently expression drops as the valves mature (33).…”

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confidence: 99%

Endoglin Is an Accessory Protein That Interacts with the Signaling Receptor Complex of Multiple Members of the Transforming Growth Factor-β Superfamily

Barbara

Wrana

Letarte³

1999

Journal of Biological Chemistry

Self Cite

527

411

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Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-␤1 and -␤3, and coprecipitates with the Ser/Thr kinase signaling receptor complex by affinity labeling of endothelial and leukemic cells. The present study shows that in addition to TGF-␤1 and -␤3, endoglin interacts with activin-A, bone morphogenetic protein (BMP)-7, and BMP-2 but requires coexpression of the respective ligand binding kinase receptor for this association. Endoglin cannot bind ligands on its own and does not alter binding to the kinase receptors. It binds TGF-␤1 and -␤3 by associating with the TGF-␤ type II receptor and interacts with activin-A and BMP-7 via activin type II receptors, ActRII and ActRIIB, regardless of which type I receptor partner is coexpressed. However, endoglin binds BMP-2 by interacting with the ligand binding type I receptors, ALK3 and ALK6. The formation of heteromeric signaling complexes was not altered by the presence of endoglin, although it was coprecipitated with these complexes. Endoglin did not interact with BMP-7 through complexes containing the BMP type II receptor, demonstrating specificity of its action. Our data suggest that endoglin is an accessory protein of multiple kinase receptor complexes of the TGF-␤ superfamily.The TGF-␤ 1 superfamily of structurally related peptides includes the TGF-␤ isoforms, ␤1, ␤2, ␤3, and ␤5, the activins and the bone morphogenetic proteins (BMPs). TGF-␤-like factors are a multifunctional set of growth and differentiation factors conserved among flies, frogs, and mammals (reviewed in Refs. 1-4). These factors control biological processes such as embryogenesis, organogenesis, morphogenesis of tissues like bone and cartilage, vasculogenesis, wound repair and angiogenesis, hematopoiesis, and immune regulation (reviewed in Refs. 2 and 4 -8). Signaling by ligands of the TGF-␤ superfamily is mediated by a high affinity, ligand-induced, heteromeric complex consisting of related Ser/Thr kinase receptors divided into two subfamilies, type I and type II (3). Formation of this high affinity complex is essential, as the type II receptor transphosphorylates and activates the type I receptor in a Gly/Ser-rich region (9 -11). The type I receptor in turn phosphorylates and transduces signals to a novel family of recently identified downstream targets, termed Smads (12, 13).Although the cooperativity between two kinase receptors is a general signaling mechanism for the TGF-␤ superfamily, where the type I receptors are considered the signal transducing receptors, ligand binding ability is not restricted to receptor type. For TGF-␤ and activin, the type II receptors T␤RII and ActRII or ActRIIB, respectively, are known to bind ligand independently (14 -16), while the corresponding type I receptors ALK5 (activin receptor-like kinase; T␤RI) or ALK4 (ActRIB) require the coexpression of the appropriate type II receptors (9,(17)(18)(19)(20)(21). The BMP family differs in this respect as the BMP type I receptors, ALK3 (BMPRI) and ALK6 (BMPRIB), can bind BMP-2 and B...

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Localization of Endoglin, a Transforming Growth Factor-β Binding Protein, and of CD44 and Integrins in Placenta during the First Trimester of Pregnancy1

Cited by 109 publications

References 38 publications

Angiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia

Angiogenic factors and natural killer (NK) cells in the pathogenesis of preeclampsia

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Endoglin Is an Accessory Protein That Interacts with the Signaling Receptor Complex of Multiple Members of the Transforming Growth Factor-β Superfamily

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