Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1β secretion and hypertension via the NLRP3 inflammasome

Ozeki, Ayae; Oogaki, Yuka; Henmi, Yuka; Karasawa, Tadayoshi; Takahashi, Masafumi; Takahashi, Hironori; Ohkuchi, Akihide; Shirasuna, Koumei

doi:10.1097/hjh.0000000000002981

Cited by 15 publications

(17 citation statements)

References 51 publications

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“…Along similar lines, Weel et al reported that PreE women had significantly higher placental expression of NLRP3, caspase-1, and IL-1β compared to normotensive women [21]. In addition to uterine and placental tissues expressing NLRP3, a recent study by Ozeki et al reported that human umbilical vein endothelial cells (HUVECs) isolated directly from women with PreE had evidence of a greater NLRP3 response relative to HUVECs isolated from normotensive women [33], suggesting that circulating factors, in particular S100A9, directly stimulate NLRP3 activity in endothelial cells.…”

Section: Nlrp3 and Preementioning

confidence: 86%

Preeclampsia and COVID-19: the Role of Inflammasome Activation

et al. 2022

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Purpose of ReviewIt is well established that controlled immune activation and balance is critical for women's reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women's reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders.Recent Findings Increased activation of inflammasome is associated with multiple women's health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19. Summary The role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE. Keywords Inflammasome • Preeclampsia • COVID-19 • NLRP3This article is part of the Topical Collection on Preeclampsia

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Section: Nlrp3 and Preementioning

confidence: 86%

Preeclampsia and COVID-19: the Role of Inflammasome Activation

et al. 2022

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“…Recent studies showed that SLC6A9 [99], FKBP1B [100], S100A12 [101], SLC6A19 [102], TXN (thioredoxin) [103], TLR9 [104], HP (haptoglobin) [105], ARG1 [106], PINK1 [107], B2M [108], C5AR1 [109], MYADM (myeloid associated differentiation marker) [110], CBS (cystathionine beta-synthase) [111], GPX1 [112], SIAH2 [113], PRDX2 [114], RDH8 [115], CYP11B2 [116], RARRES2 [117], NOX1 [118], IL33 [119], OTC (ornithine transcarbamylase) [120], CYP1A1 [121], NFATC4 [122], TSLP (thymic stromal lymphopoietin) [123], WNT4 [124], MGP (matrix Gla protein) [125], FGFBP1 [126], GHR (growth hormone receptor) [127], ERBB3 [128], GFAP (glial fibrillary acidic protein) [129], CCDC40 [130], CACNB2 [131], CD34 [132], NOTCH3 [133], TERT (telomerase reverse transcriptase) [134], GNB3 [135], TP73 [136], RYR2 [137], ENPEP (glutamyl aminopeptidase) [138], SCN7A [139], WNK4 [140], SFRP5 [141], GDF15 [142], CAV1 [143], KCNA5 [144], FOXC1 [145], ASIC1 [146], VASH2 [147], CXCL8 [148], PAPPA2 [149], KCNMA1 [150], LOX (lysyl oxidase) [151], SPARCL1 [152] and CYP3A5 [153] might have the potential to be used as diagnostic biomarkers of hypertension. Previous studies have reported that RHD (Rh blood group D antigen) [154], S100A12 [155], TXN (thioredoxin) [156], TLR9 [157], S100P [158], TAGLN2 [159], S100A9 [160], CA1 [161], HP (haptoglobin) [162], RPL39 [163], F5 [164], PINK1 [165], B2M [166], S100A11 [167], SLC4A1 [168], CBS (cystathionine beta-sy...…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Bipolar disorder (BD), also known as psychiatric disorder, affects millions of people all over the world. The aim of this investigation was to screen and verify hub genes involved in BD as well as to explore potential molecular mechanisms. The next generation sequencing (NGS) dataset GSE124326 was downloaded from the Gene Expression Omnibus (GEO) database, which contained 480 samples, including 240 BD and 240 normal controls. Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. A protein–protein interaction (PPI) network and module analysis were used to identify hub genes. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed. Receiver operating characteristic curve (ROC) analysis was used to validate hub genes. In this work, 957 DEGs, including 477 up regulated and 480 down regulated, were obtained from NGS data. The GO and pathway enrichment analyses of the DEGs showed that the up regulated genes were enriched in the neutrophil degranulation, immune system, transport, cytoplasm and enzyme regulator activity, and the down regulated genes were enriched in extracellular matrix organization, diseases of metabolism, multicellular organismal process, cell periphery and metal ion binding. Finally, through analyzing the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes UBB, UBE2D1, TUBA1A, RPL11, RPS24, NOTCH3, CAV1, CNBD2, CCNA1 and MYH11 by the Cytoscape software. The current investigation illustrates a characteristic NGS data in BD, which might contribute to the interpretation of the progression of BD and provide novel biomarkers and therapeutic targets for BD.

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“…These ndings indicate that the NLRP3 in ammasome has an important function in hypertension in pregnant women. Ozeki et al demonstrated that S100A9 acts as a danger signal to activate the NLRP3 in ammasome in the placenta, associating with hypertension during pregnancy [37].…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome in peripheral blood monocytes as a risk factor for early onset pre-eclampsia

Guo

et al. 2022

Preprint

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Introduction As a leading cause of pregnancy and fetal mortality, pre-eclampsia impacts about 5–8% of pregnancies globally. To date, few studies have focused on the role played by NLRP3 in peripheral blood in early onset PE. In this study, we investigated whether NLRP3 expression in monocytes before 20 weeks of gestation was associated with an increased risk of early onset PE. Methodology During the study period from 2019 to 2021, women with singleton pregnancies were enrolled in this prospective study at the General Hospital of Northern Theater Command. A generalized additive model (GAM) and logistic regression models were applied to determine any association between NLRP3 and the risk of early onset PE. Results In total, 571 and 48 subjects were included in the control and pre-eclampsia groups, respectively. The GAM and logistic regression models showed that NLRP3 was a significant factor for PE occurrence. The area under the curve, accuracy, specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.86, 0.82, 0.95, 0.72, 15.17, 0.29, and 52.0, respectively. Conclusion The monitoring for NLRP3 in peripheral blood may be a potential, prospectively identifying risk factor for preeclampsia.

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Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1β secretion and hypertension via the NLRP3 inflammasome

Cited by 15 publications

References 51 publications

Preeclampsia and COVID-19: the Role of Inflammasome Activation

Preeclampsia and COVID-19: the Role of Inflammasome Activation

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

NLRP3 inflammasome in peripheral blood monocytes as a risk factor for early onset pre-eclampsia

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