Promoter methylation changes and vascular dysfunction in pre-eclamptic umbilical vein

Gao, Qinqin; Fan, Xiaoning; Xu, Tao; Li, Huan; He, Yuxiu; Yang, Yuxian; Chen, Jie; Ding, Hongmei; Tao, Jianying; Xu, Zhice

doi:10.1186/s13148-019-0685-2

Cited by 15 publications

(10 citation statements)

References 48 publications

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“…Global placental methylation, accounting for higher SBP and DBP, was related to PE susceptibility . There are also several studies which have provided evidence that the PE pathogenesis is correlated with the promoter methylation status of relevant genes . Based on the effect of promoter region DNA methylation on regulating the expression of genes related to invasiveness of trophoblasts, the importance of promoter methylaytion in gene expression during normal pregnancy and potential of their deregulation in the development of PE have been reported previously …”

Section: Discussionmentioning

confidence: 98%

“…51 There are also several studies which have provided evidence that the PE pathogenesis is correlated with the promoter methylation status of relevant genes. [52][53][54] Based on the effect of promoter region DNA methylation on regulating the expression of genes related to invasiveness of trophoblasts, the importance of promoter methylaytion in gene expression during normal pregnancy and potential of their deregulation in the development of PE have been reported previously. [55][56][57] In the current study, there found no effect of placental H19 rs3741219 and rs2107425 polymorphisms on PE susceptibility.…”

Section: Discussionmentioning

confidence: 99%

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The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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The effect of DNA methylation on gene expression triggered it as a susceptibility factor in various diseases including preeclampsia (PE). The pathogenesis of PE is closely associated with the methylation status and genetic variants of relevant genes. Therefore, the aim of the study was to investigate the possible impacts of the placental DNA methylation and rs3741219, rs217727, and rs2107425 polymorphisms of the H19 gene on the PE susceptibility as well as the its mRNA expression. Moreover, eight haplotypes of three loci in the H19 gene were analyzed. In this case‐control study, the placentas of 107 preeclamptic and 113 non‐preeclamptic women were collected after delivery. The methylation status was assessed by methylation‐specific polymerase chain reaction (PCR). The H19 polymorphisms were genotyped using polymerase chain reaction‐restriction fragment length polymorphism or amplification refractory mutation system‐polymerase chain reaction methods. The quantitative real time PCR was used for mRNA expression assay. The placental H19 rs3741219 and rs2107425 polymorphisms were not associated with PE. However, H19 rs217727CT and TT genotypes might be associated with a 9.2‐ and 17.7‐fold increased risk of PE, respectively. The Trs3741219 Crs217727 Crs2107425 and Trs3741219 Crs217727 Trs2107425 haplotypes were significantly lower, whereas the Trs3741219 Trs217727 Crs2107425 and Crs3741219 Trs217727 Crs2107425 haplotypes were significantly higher in PE women. Promoter but not upstream region hypermethylation of H19 gene could be led to decreased risk of PE (MM vs. UM + UU). No significant difference was observed in the placental mRNA expression between two groups. The H19 expression was significantly higher in women with unmethylated (UU), compared to methylated promoter (MM). The H19 expression was 17‐ and 15‐fold higher in H19‐rs2107425 CC and CT genotypes in PE women. In conclusion, the H19 rs2107425 polymorphism was associated with a higher risk of PE and increased H19 mRNA expression. The promoter hypermethylation of H19 gene was associated with a lower risk of PE and decreased H19 mRNA expression.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

et al. 2019

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“…PE is a multisystem disorder of pregnancy with uncertain etiology and pathophysiology, and its primary clinical presentation is hypertension and proteinuria after 20 weeks of gestation. 22 It affects 5–8% of all pregnancies worldwide and is an independent significant risk factor for both maternal and fetal morbidity. 23,24 Generalized arteriolar vasospasm is a key factor in PE.…”

Section: Discussionmentioning

confidence: 99%

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Shi,

Kong,

Miao

et al. 2023

Exp Biol Med (Maywood)

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Pre-eclampsia (PE) is a severe pregnancy complication characterized by impaired trophoblast invasion and spiral artery remodeling and can have serious consequences for both mother and child. Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is involved in numerous tumor-related biological processes. However, the biological action and underlying mechanisms of PPP1R3G in PE progression remain unclear. We used western blotting and immunohistochemistry to investigate PPP1R3G expression in gestational age-matched pre-eclamptic and normal placental tissues. After lentivirus transfection, wound-healing, Transwell, cell-counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and TdT mediateddUTP Nick End Labeling (TUNEL) assays were used to assess trophoblast migration, invasion, proliferation, and apoptosis, respectively. The relative expression levels of PPP1R3G and the proteins involved in the Akt signaling pathway were determined using western blotting. The results showed that PPP1R3G levels were significantly lower in the placental tissues and GSE74341 microarray of the PE group than those of the healthy control group. We also found that neonatal weight and Apgar score were lower at birth, and peak systolic blood pressure and diastolic blood pressure were higher in the PE group than in the non-PE group. In addition, PPP1R3G knockdown decreased p-Akt/Akt expression and inhibited migration, invasion, and proliferation in HTR-8/SVneo trophoblasts but had no discernible effect on cell apoptosis. Furthermore, PPP1R3G positively regulated matrix metallopeptidase 9 (MMP-9), which was downregulated in placental tissues of pregnant women with PE. These results provided the first evidence that the reduced levels of PPP1R3G might contribute to PE by suppressing the invasion and migration of trophoblasts and targeting the Akt/MMP-9 signaling pathway.

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“…The primer sequences against the predicted CpG island sequence were designed and listed in Table 1 . Genomic DNA was extracted from primary SMCs of TA, MA, MCA, or PA, and subjected to bisulfite conversion using EZ DNA Methylation™-GOLD Kit (Zymo Research) for sequencing ( 14 , 15 ). After polymerase chain reaction amplification, products were sequenced by Hiseq 2000 (Illumina, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Unveiling the Role of DNA Methylation in Vascular CACNA1C Tissue–Specific Expression

Zhao

Lei

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveCalcium voltage-gated channel subunit alpha1 C (CACNA1C) plays a critical role in many vascular physiological and pathological processes. Determining its tissue-specific expression pattern and clarifying the underlying molecular mechanisms are necessary and meaningful.MethodsWe selected several representative vessels from normal male Sprague-Dawley rats. Vessel tissue or primary vascular smooth muscle cells were isolated for vascular function, electrophysiology, gene expression and promoter methylation studies.ResultsWe found CACNA1C had tissue-specific expressions in vessels. The specific manifestations were as follows: CACNA1C expression was highest in thoracic aorta, second lowest in middle cerebral and pulmonary artery, and lowest in mesenteric artery. Excitingly, an opposing trend was observed between CACNA1C expression and its promoter methylation.ConclusionsThis study was the first report to indicate that DNA methylation could be involved in regulating CACNA1C tissue-specific expressions and vasoconstriction function in vascular system. This study not only provided more information for further understanding the physiological characteristics of vascular CACNA1C expressions, also strengthened the idea that DNA methylation plays important roles in regulating vascular smooth muscle cells function and the consequent occurrence of vascular diseases.

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Promoter methylation changes and vascular dysfunction in pre-eclamptic umbilical vein

Cited by 15 publications

References 48 publications

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

The effects of placental long noncoding RNA H19 polymorphisms and promoter methylation on H19 expression in association with preeclampsia susceptibility

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway

Unveiling the Role of DNA Methylation in Vascular CACNA1C Tissue–Specific Expression

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