Mechanism of JNK signal regulation by placental HSP70 and HSP90 in endothelial cell during preeclampsia

Perumal, Ekambaram; Uthra, Venkatraman; Lavanya, S.

doi:10.3109/15376516.2012.673091

Cited by 15 publications

(10 citation statements)

References 44 publications

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“…The expression of HSP90 could be polemic because apparently it is related with the disease progression and also placenta location [68]. However several authors had being found an increment in the placenta expression of HSP90 in PE [68–70] at mRNA and protein levels. Moreover, this increment can be a protective reaction that is stimulated by HIF1A [71] and consequently connected to disease progression as described in [68].…”

Section: Discussionmentioning

confidence: 99%

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

et al. 2017

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BackgroundPreeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis.MethodsWe firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways.ResultsThe consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism.ConclusionOur results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-017-0286-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

et al. 2017

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“…Meanwhile, the observed increase in BAG3 gene expression is probably due to the compensatory mechanisms or anti-apoptotic properties of the protein encoded by this locus. This assumption is supported by a statistically significant increase in the expression of the Hsp70 and Hsp90 heat shock proteins, heat shock factor 1 (HSF1), and Bcl-2 anti-apoptotic factor in endothelial cells of the placenta of PE patients as compared to females with normotensive pregnancy [62]. Moreover, the analysis of the proteome of placental tissue from females with physiological and complicated pregnancies has revealed the significance of stress-inducible proteins, including Hsp70, in the pathogenesis of PE [63].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Placental Tissue Transcriptome of Normal and Preeclampsia Complicated Pregnancies

et al. 2014

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Preeclampsia is one of the most severe gestational complications which is one of the leading causes of maternal and perinatal morbidity and mortality. A growth in the incidence of severe and combined forms of the pathology has been observed in recent years. According to modern concepts, inadequate cytotrophoblast invasion into the spiral arteries of the uterus and development of the ischemia-reperfusion syndrome in the placental tissue play the leading role in the development of preeclampsia, which is characterized by multipleorgan failure. In this regard, our work was aimed at studying the patterns of placental tissue transcriptome that are specific to females with PE and with physiological pregnancy, as well as identifying the potential promising biomarkers and molecular mechanisms of this pathology. We have identified 63 genes whose expression proved to differ significantly in the placental tissue of females with PE and with physiological pregnancy. A cluster of differentially expressed genes (DEG) whose expression level is increased in patients with preeclampsia includes not only the known candidate genes that have been identified in many other genome-wide studies (e.g., LEP, BHLHB2, SIGLEC6, RDH13, BCL6), but also new genes (ANKRD37, SYDE1, CYBA, ITGB2, etc.), which can be considered as new biological markers of preeclampsia and are of further interest. The results of a functional annotation of DEG show that the development of preeclampsia may be related to a stress response, immune processes, the regulation of cell-cell interactions, intracellular signaling cascades, etc. In addition, the features of the differential gene expression depending on preeclampsia severity were revealed. We have found evidence of the important role of the molecular mechanisms responsible for the failure of immunological tolerance and initiation of the pro-inflammatory cascade in the development of severe preeclampsia. The results obtained elaborate the concept of the pathophysiology of preeclampsia and contain the information necessary to work out measures for targeted therapy of this disease. ;

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“…Altered HSP90 expression has been reported in placental endothelial cells, and placental tissues of preeclamptic and intrauterine growth restriction affected pregnancy (35,14,53).…”

Section: Discussionmentioning

confidence: 98%

Oxygen governs Galβ1–3GalNAc epitope in human placenta

Ermini

Bhattacharjee

Spagnoletti

et al. 2013

American Journal of Physiology-Cell Physiology

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It is becoming increasingly apparent that the dynamics of glycans reflect the physiological state of cells involved in several cell functions including growth, response to signal molecules, migration, as well as adhesion to, interaction with, and recognition of other cells. The presence of glycoconjugates in human placenta suggests their major role in maternal-fetal exchanges, intercellular adhesion, cellular metabolism, and villous vessel branching. Although several studies have described glycoconjugate distribution in the human placenta descriptions of their physiological function and control mechanisms during placental development are lacking. In this study we investigated the developmental distribution and regulation of placental core 1 O- and N-glycans focusing on early and late first trimester human pregnancy. To define the control mechanisms of the oligosaccharide chains during early placentation process, chorionic villous explants and human trophoblast cell lines were exposed to various oxygen levels. We found that oxygen tension regulates changes in core-1 O-glycan (the disaccharide Galβ1-3GalNAc) epitope expression levels. Moreover, by double affinity chromatography and subsequent analysis with mass spectrometry, we identified in the heat shock protein 90-α (HSP90α) a good candidate as carrier of the Galβ1-3GalNAc epitope at low oxygen tension. Our results support a fundamental role of oxygen tension in modulating glycosylation of proteins during placental development.

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Mechanism of JNK signal regulation by placental HSP70 and HSP90 in endothelial cell during preeclampsia

Cited by 15 publications

References 44 publications

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

Analysis of the Placental Tissue Transcriptome of Normal and Preeclampsia Complicated Pregnancies

Oxygen governs Galβ1–3GalNAc epitope in human placenta

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