Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Xiong, Jiantuan; Ding, Ning; Gao, Tingting; Wang, Yanhua; W, Guo; Zhang, Hui; Li, Fan; Sun, Jianmin; Yang, Xia; Wu, Kai; Zhang, Huiping; Jiang, Yideng

doi:10.1002/jcb.27101

Cited by 11 publications

(8 citation statements)

References 35 publications

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“…Hence, the miR-148/152 family may contribute to PE via modulation of DNA methylation patterns that leads to aberrant expression of downstream targets involved in metabolic and immune pathways (Figure 3). In agreement with the findings by Yang et al [42], a separate study in L-NAME-induced PE rats also reported a downregulation of DNMT1 in placentas and in hypoxia-treated trophoblasts [233]. In contrast, a study examining PE-like mice exposed to Bisphenol A (BPA) found a significant elevation in DNMT1 placental protein levels and an increase in DNMT1 expression in HTR-8/SVneo trophoblast cells exposed to BPA [234].…”

Section: Gene Targets Of Mir-148/152supporting

confidence: 81%

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

et al. 2020

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Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

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Section: Gene Targets Of Mir-148/152supporting

confidence: 81%

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

et al. 2020

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“…It has been found that increased Ero1α is involved in the development of ER stress-induced vascular endothelial dysfunction [20] and cardiomyopathy [21,22]. Upregulation of Ero1α exacerbates ER stress, and leads to cell death [23][24][25]. Ero1α is critical for ER stress-induced apoptosis of macrophages in insulin-resistant obese mice [26], and macrophage apoptosis occurs in advanced plaque induced by HHcy [12].…”

Section: Introductionmentioning

confidence: 99%

The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis

Zhang

Zhu

et al. 2021

Atherosclerosis

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Background and aims: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1α (Ero1α) is critical for ER stress-induced apoptosis. We hypothesized that Ero1α may contribute to ER-stress induced macrophage apoptosis and plaque stability in advanced atherosclerotic lesions by HHcy. Methods: Apoe − /− mice were maintained on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy atherosclerotic models. The role of Ero1α in atherosclerotic plaque stability, macrophage apoptosis and ER stress were monitored in the plaque of aortic roots in HHcy Apoe − /− mice with or without silence or overexpression of Ero1α through lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of Ero1α on ER stress dependent apoptosis in the presence of HHcy. Results: Atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in Apoe − /− mice by high Hcy diet, accompanied by the upregulation of Ero1α expression and ER stress. Inhibition of Ero1α prevented macrophage apoptosis and atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1α deficiency, but enhanced by Ero1α overexpression. Conclusions: Hcy, via upregulation of Ero1α expression, activates ER stress-dependent macrophage apoptosis to promote vulnerable plaque formation in atherosclerosis. Ero1α may be a potential therapeutic target for atherosclerosis induced by Hcy.

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“…A large number of studies have shown that DNA methylation occurs in all living creatures and plays an important role in many diseases. , Meanwhile, as the only family of proteases that can catalyze the process of DNA methylation, DNMTs also play an important role in gene expression regulation during pathological processes . Previous studies suggested that DNA methylation activated by DNMTs resulted in the silencing of gene expression, which induced cell apoptosis, inflammation, oxidative stress, etc., , while the inhibition of DNMTs could effectively alleviate these phenomena. There are a lot of studies on DNA methylation in AFB 1 toxicity and the development of hepatocellular carcinoma (HCC) .…”

Section: Introductionmentioning

confidence: 99%

Aflatoxin B₁ Induces Immunotoxicity through the DNA Methyltransferase-Mediated JAK2/STAT3 Pathway in 3D4/21 Cells

Zhou

Gan

Hou

et al. 2019

J. Agric. Food Chem.

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As the most toxic mycotoxin of all of the fungal toxins, aflatoxin B1 (AFB1) has carcinogenesis, heptotoxicity, and immunotoxicity. DNA methylation plays a critical role in gene expression regulation of the pathological process. However, the relationship between DNA methylation and AFB1-induced immunotoxicity was not yet reported. Therefore, the objectives of this study were to verify AFB1-induced immunotoxicity and investigate the potential role of the DNA methyltransferase (DNMT) family in AFB1-induced immunotoxicity and the pathway mechanism in 3D4/21 cells. The results showed that AFB1 could induce cytotoxicity, apoptosis, pro-inflammatory cytokine expression, DNA damage, and oxidative stress and decrease phagocytotic capacity. Meanwhile, the levels of DNMT1 and DNMT3a were significantly increased in 0.04 and 0.08 μg/mL AFB1 compared to the control. Inhibition of DNMT1 and DNMT3a by 5-Aza-2dc could reverse changes of the above parameters. Further, the JAK2/STAT3 pathway was significantly activated in 0.04 μg/mL AFB1. Inhibition of p-JAK2 and p-STAT3 by AG490 could alleviate AFB1-induced immunotoxicity. Moreover, inhibition of DNMT1 and DNMT3a by 5-Aza-2dc could suppress the phosphorylation of JAK2 and STAT3. Taken together, AFB1-induced immunotoxicity is related to the JAK2/STAT3 pathway mediated by DNMTs in 3D4/21 cells.

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Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Cited by 11 publications

References 35 publications

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis

Aflatoxin B₁ Induces Immunotoxicity through the DNA Methyltransferase-Mediated JAK2/STAT3 Pathway in 3D4/21 Cells

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Hypermethylation of endoplasmic reticulum disulfide oxidase 1α leads to trophoblast cell apoptosis through endoplasmic reticulum stress in preeclampsia

Cited by 11 publications

References 35 publications

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis

Aflatoxin B1 Induces Immunotoxicity through the DNA Methyltransferase-Mediated JAK2/STAT3 Pathway in 3D4/21 Cells

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Aflatoxin B₁ Induces Immunotoxicity through the DNA Methyltransferase-Mediated JAK2/STAT3 Pathway in 3D4/21 Cells