Preeclamptic plasma stimulates the expression of miRNAs, leading to a decrease in endothelin-1 production in endothelial cells

Caldeira-Dias, Mayara; Luizon, Marcelo R.; Deffune, Elenice; Tanus‐Santos, José Eduardo; Freire, Paula Paccielli; Carvalho, Robson Francisco; Bettiol, Heloísa; Cardoso, Viviane Cunha; Barbieri, Marco Antônio; Cavalli, Ricardo Carvalho; Sandrim, Valéria C.

doi:10.1016/j.preghy.2018.03.001

Cited by 20 publications

(12 citation statements)

References 45 publications

(74 reference statements)

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“…Furthermore, overexpression of let-7 in endothelial cells from PE notably correlated with the expression of genes related to endothelial dysfunction and pathophysiology development, suggesting a critical role of let-7 in PE. 28 In addition, low expression of FOXO1 was found in villous trophoblasts, while overexpression of FOXO1 contributed to abnormal trophoblast differentiation and inhibition of apoptosis in mild and severe PE. 29 More importantly, an increase of FOXO1 was reported to promote adhesion and migration of trophoblast cells, thus preventing the progression of PE.…”

Section: Discussionmentioning

confidence: 99%

MSC-Secreted Exosomal H19 Promotes Trophoblast Cell Invasion and Migration by Downregulating let-7b and Upregulating FOXO1

Chen

Ding

Wei

et al. 2020

Molecular Therapy - Nucleic Acids

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Exosomes perform important functions for intercellular communication through extracellular signaling pathways, leading to the regulation of important biological processes, including cell proliferation, but also systemic dysfunctions such as preeclampsia (PE). However, the inhibitory effects of mesenchymal stem cell (MSCs)-derived exosomes in PE remain largely unknown. Thus, we assessed the possibility that exosomes could transport long non-coding RNA H19 and the correlation between H19 and the apoptosis of trophoblast cells. The expression of microRNA let-7b and forkhead box protein O1 (FOXO1) was characterized in placental tissues of PE patients. Gain-and lossof-function experiments were performed to examine the roles of FOXO1 and let-7b in trophoblast cells. Interactions between let-7b and H19 as well as between let-7b and FOXO1 were confirmed by a dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation. HTR-8/SVneo cells were co-cultured with exosomes derived from MSCs overexpressing H19, followed by invasion, migration, and apoptosis assessments of trophoblast cells. We found that let-7b was highly expressed and FOXO1 was poorly expressed in placental tissues of PE patients. Furthermore, H19 acts as a competitive endogenous RNA against let-7b, and let-7b directly targeted FOXO1. Moreover, H19 could be transferred to trophoblast cells via MSCsecreted exosomes. MSC-derived exosomes overexpressing H19 decreased let-7b, increased FOXO1, and activated the protein kinase B (AKT) signaling pathway, thus increasing invasion and migration and inhibiting apoptosis of trophoblast cells. These results suggest that MSC-derived exosomes overexpressing H19 may be a novel direction for therapeutic strategies against PE.

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Section: Discussionmentioning

confidence: 99%

MSC-Secreted Exosomal H19 Promotes Trophoblast Cell Invasion and Migration by Downregulating let-7b and Upregulating FOXO1

Chen

Ding

Wei

et al. 2020

Molecular Therapy - Nucleic Acids

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“…miRNAs impact on the posttranscriptional regulation of the ET‐1 gene (EDN1) . In human umbilical vein endothelial cell (HUVEC) incubated with plasma in PE women, resulting in an elevated level of miRNAs 125a, 125b, Let‐7a, Let‐7b, and Let‐7c . As well as Dias et al demonstrated that ET‐1 level was significantly decreased (approximately 25%), after transfection of miRNA mimic Let‐7b in the HUVEC supernatants.…”

Section: Epigenetic Changes In Pementioning

confidence: 98%

The role of epigenetic changes in preeclampsia

et al. 2019

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Preeclampsia (PE) is a disorder affecting 2–10% of pregnancies and has a major role for perinatal and maternal mortality and morbidity. PE can be occurred by initiation of new hypertension combined with proteinuria after 20 weeks gestation, as well as various reasons such as inflammatory cytokines, poor trophoblast invasion can be related with PE disease. Environmental factors can cause epigenetic changes including DNA methylation, microRNAs (miRNAs), and histone modification that may be related to different diseases such as PE. Abnormal DNA methylation during placentation is the most important epigenetic factor correlated with PE. Moreover, changes in histone modification like acetylation and also the effect of overregulation or low regulation of miRNAs or long noncoding RNAs on variety signaling pathways can be resulted in PE. The aim of this review is to describe of studies about epigenetic changes in PE and its therapeutic strategies.

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“…Furthermore, endothelin‐1 (ET‐1), an endothelium‐derived vasoconstrictor in SMCs, may function in the adaptive vasodilation during pregnancy 13 . In recent years, ET‐1 has been reported to be regulated post‐transcriptionally by various miRNAs 14 . For instance, miR‐199 is identified as a negative regulator of ET‐1 expression in human ECs 15 .…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA MALAT1 contributes to pregnancy‐induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR‐150‐5p/ET‐1 axis

Zhao

et al. 2020

FASEB j.

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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/ miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1β), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction. Furthermore, silencing MALAT1 could alleviate the hypertensive symptoms of RUPP-induced rat models. Taken conjointly, the upregulation of MALAT1 can reduce the expression of ET-1 by competitively binding to miR-150-5p, which enhances the expression of ETBR via the activation of the NF-κB pathway in SMCs, thus exacerbating the hypertensive symptoms in the RUPP-induced rat models. K E Y W O R D Sendothelial cells, endothelin-1, metastasis-associated lung adenocarcinoma transcript 1, microRNA-150-5p, NF-κB pathway, pregnancy-induced hypertension, smooth muscle cells

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Preeclamptic plasma stimulates the expression of miRNAs, leading to a decrease in endothelin-1 production in endothelial cells

Cited by 20 publications

References 45 publications

MSC-Secreted Exosomal H19 Promotes Trophoblast Cell Invasion and Migration by Downregulating let-7b and Upregulating FOXO1

MSC-Secreted Exosomal H19 Promotes Trophoblast Cell Invasion and Migration by Downregulating let-7b and Upregulating FOXO1

The role of epigenetic changes in preeclampsia

Long noncoding RNA MALAT1 contributes to pregnancy‐induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR‐150‐5p/ET‐1 axis

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