A Proteomic Analysis of Placental Trophoblastic Cells in Preeclampsia–Eclampsia

Ma, Kaidong; Jin, Hong; Hu, Rong; Xiong, Yan; Zhou, Shu‐Feng; Peng, Ting; Chen, Yan; Yang, Yan; Yang, Pengyuan; Li, Xiaotian

doi:10.1007/s12013-013-9792-4

Cited by 30 publications

(17 citation statements)

References 45 publications

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“…These placental abnormalities are potentially caused by the lack of stable adhesion between cytotrophoblasts and Lama5. Moreover, human term placenta from preeclamptic pregnancies have lower expression levels of laminin compare to those of normal pregnancies . The expressions of laminin alpha 2 appears to also be downregulated in the basal plate of preeclamptic term placenta .…”

Section: Introductionmentioning

confidence: 91%

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Kuo

Guo

Cabrera-Luque

et al. 2018

J Biomedical Materials Res

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Fetal cytotrophoblast invasion of maternal decidual vasculature is necessary to normal pregnancy. In preeclampsia, there is shallow invasion and abnormal remodeling of the uterine vasculature that lead to significant maternal and perinatal morbidity and mortality. The placental basement membrane (BM) proteins (e.g., laminin and collagen) has been implicated in the development of placenta while the level of laminin is significantly lower in preeclampsia. However, there are very limited studies, if any, on the effect of extracellular matrix (ECM) microenvironment on the invasion of cytotrophoblast. In this study, we hypothesized that placental BM proteins are required for effective cytotrophoblast invasion. Using proteomics, we found that more than 80% of ECM proteins in placental basal plate (pECM) were BM proteins. In addition to upregulating expressions of MMP2 (1.5-fold) and MMP9 (6.3-fold), pECM significantly increased the motility rates of cytotrophoblasts by 13-fold (from 5.60 ± 0.95 to 75.5 ± 21.8 µm/day) to achieve an effective invasion rate that was comparable to in vivo results. Treatments with PI3K inhibitors completely removed the pECM-enhanced invasive phenotypes and genotypes of cytotrophoblasts, suggesting its dominant role in cytotrophoblast-ECM interactions. Our results described, for the first time, the substantial effects of the ECM microenvironment on regulating cytotrophoblast invasion, an area that is less investigated but appear to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work that fabricates organ models with organ-specific ECM can be an attractive option to screen and develop novel therapeutics and biomarkers not only in preeclampsia but also other diseases such as cancer metastasis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1476-1487, 2018.

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Section: Introductionmentioning

confidence: 91%

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Kuo

Guo

Cabrera-Luque

et al. 2018

J Biomedical Materials Res

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“…For comparison purposes, we used the equivalent cells that were microdissected from the placentas of nPTB cases. Previous studies that used laser microdissection and placental samples were aimed at protein analyses [85][86][87][88] or particular mRNA targets. 89 To our knowledge, this is the first time that such an approach has been used with the goal of global transcriptional profiling.…”

Section: Ajogorg Obstetrics Original Researchmentioning

confidence: 99%

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Gormley

Ona

Kapidzic

et al. 2017

American Journal of Obstetrics and Gynecology

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BACKGROUND:The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. OBJECTIVE: Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. STUDY DESIGN: This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of noneprotein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. RESULTS: Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-typeespecific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy

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“…Pregnancy is a complex and highly regulated process in which the placenta plays an essential role . It consists mainly of trophoblastic cells, which differentiate along two pathways to give rise to either villous or extravillous trophoblasts (EVTs) .…”

Section: Several Differentially Expressed Proteins Between the Bewo Amentioning

confidence: 99%

Comparative proteomic analysis of trophoblast cell models reveals their differential phenotypes, potential uses, and limitations

et al. 2017

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Trophoblastic cell lines are widely used in in vitro studies of placental function as a surrogate for primary trophoblasts. To date, no reference proteomics dataset exists to directly compare the shared and unique characteristics of these cells. Here, we performed comparative proteomic profiling of the BeWo and HTR8/SVneo cell lines using label-free quantitative mass spectrometry. 1557 proteins were identified, which included 338 uniquely attributed to BeWo cells, and a further 304 specifically identified in HTR8/SVneo cells. Raw data is available via ProteomeXchange, identifier PDX005045. Of the 915 proteins expressed by both cell lines, 105 were of higher abundance in BeWo cells, while 199 proteins had a significantly higher expression in HTR8/SVneo cells. Comparative gene ontology of unique and up-regulated proteins revealed principal differences in cell junction/adhesion, catenin complex, spindle and microtubule associated complex, as well as cell differentiation. Our data indicates that BeWo cells express an epithelial proteome more characteristic of villous trophoblasts, whereas HTR8/SVneo cells embrace a mesenchymal phenotype, more characteristic of extravillous trophoblasts. This novel comparative proteomic profiling of these trophoblastic cell lines provides a useful platform for future investigations of placental function. This article is protected by copyright. All rights reserved.

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A Proteomic Analysis of Placental Trophoblastic Cells in Preeclampsia–Eclampsia

Cited by 30 publications

References 45 publications

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three‐dimensional bioprinted placenta model

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Comparative proteomic analysis of trophoblast cell models reveals their differential phenotypes, potential uses, and limitations

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