Knockdown of JARID2 inhibits the viability and migration of placenta trophoblast cells in preeclampsia

Jiang, Yatao; Chen, Yuqing; Chen, Yanping

doi:10.3892/mmr.2017.7011

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Additionally, the potential therapeutic significance of JARID2 in addressing Preeclampsia has been proposed. This proposition is grounded in the observed inhibitory effects of JARID2 on the viability and migration of placental trophoblast cells, as elucidated in previous research (64).…”

Section: Discussionmentioning

confidence: 64%

MicroRNA analysis of medium/large placenta extracellular vesicles in normal and preeclampsia pregnancies

Awoyemi,

Jiang,

Rahbar

et al. 2024

Front. Cardiovasc. Med.

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BackgroundPreeclampsia (PE) is a hypertensive disorder of pregnancy, affecting 2%–8% of pregnancies worldwide, and is the leading cause of adverse maternal and fetal outcomes. The disease is characterized by oxidative and cellular stress and widespread endothelial dysfunction. While the precise mechanisms are not entirely understood, the pathogenesis of PE is closely linked to placental dysfunction and, to some extent, syncytiotrophoblast extracellular vesicle release (STB-EVs). These vesicles can be divided into the less well-studied medium/large EVs (220–1,000 nm) released in response to stress and small EVs (<220 nm) released as a component of intercellular communication. The previously described production of m/lSTB-EVs in response to cellular stress combined with the overwhelming occurrence of cellular and oxidative stress in PE prompted us to evaluate the microRNAome of PE m/lSTB-EVs. We hypothesized that the microRNAome profile of m/lSTB-EVs is different in PE compared to normal pregnancy (NP), which might permit the identification of potential circulating biomarkers not previously described in PE.Methods/study designWe performed small RNA sequencing on medium/large STB-EVs isolated from PE and NP placentae using dual-lobe ex vivo perfusion. The sequencing data was bioinformatically analyzed to identify differentially regulated microRNAs. Identified microRNAs were validated with quantitative PCR analysis. We completed our analysis by performing an in-silico prediction of STB-EV mechanistic pathways.ResultsWe identified significant differences between PE and NP in the STB-EVs micro ribonucleic acid (microRNA) profiles. We verified the differential expression of hsa-miR-193b-5p, hsa-miR-324-5p, hsa-miR-652-3p, hsa-miR-3196, hsa-miR-9-5p, hsa-miR-421, and hsa-miR-210-3p in the medium/large STB-EVs. We also confirmed the differential abundance of hsa-miR-9-5p in maternal serum extracellular vesicles (S EVs). In addition, we integrated the results of these microRNAs into the previously published messenger RNA (mRNA) data to better understand the relationship between these biomolecules.ConclusionsWe identified a differentially regulated micro-RNA, hsa-miR-9-5p, that may have biomarker potential and uncovered mechanistic pathways that may be important in the pathophysiology of PE.

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Section: Discussionmentioning

confidence: 64%

MicroRNA analysis of medium/large placenta extracellular vesicles in normal and preeclampsia pregnancies

Awoyemi,

Jiang,

Rahbar

et al. 2024

Front. Cardiovasc. Med.

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“…Efficient trophoblastic infiltration forms the basis for the effective establishment of uteroplacental circulation and is key to successful pregnancy ( 33 ). Insufficient invasion and migration of trophoblast cells results in shallow embryo implantation, inadequate placental invasion and abnormal spiral artery remodeling, which are generally regarded to be major mechanisms underlying PE ( 34 ). To the best of our knowledge, the present study is the first to explore the effects of PAD4 on the invasion and migration of HTR8/SVneo cells following exposure to LPS, where PAD4 silencing promoted the invasion and migration of HTR8/SVneo cells.…”

Section: Discussionmentioning

confidence: 99%

PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF‑κB pathway

Zeng

et al. 2022

Exp Ther Med

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Preeclampsia (PE), presenting with onset hypertension and proteinuria, is a pregnancy-specific disorder that can result in maternal and fetal morbidity and mortality. Insufficient trophoblast invasion and migration has been considered to be an important cause of this disease. The present study aimed to investigate the role of peptidyl arginine deiminase 4 (PAD4), whose knockdown has been previously indicated to reduce inflammation and susceptibility to pregnancy loss in mice, in the development of PE in vitro. Lipopolysaccharide (LPS) was used to treat a human trophoblast cell line (HTR8/SVneo). After PAD4 silencing via transfection with short hairpin RNA against PAD4, the concentrations of inflammatory factors IL-6, IL-12 and monocyte chemoattractant protein (MCP)-1 were measured using ELISA. Cell viability was also measured using Cell Counting Kit-8 assay. HTR8/SVneo cell invasion and migration were detected using Transwell and wound healing assays, respectively. Western blotting was used to measure the expression of citrullinated NF-κB essential modulator (NEMO) and nuclear NF-κB p65 protein levels. TNF-α was applied for evaluating the potential regulatory effects of PAD4 on NF-κB in LPS-stimulated HTR8/SVneo cells. LPS increased the levels of IL-6, IL-12 and MCP-1 and reduced the migration and invasion of HTR8/SVneo cells. PAD4-knockdown was found to markedly reduce the levels of IL-6, IL-12 and MCP-1 secretion. HTR8/SVneo cell invasion and migration was also significantly elevated after PAD4 silencing following LPS exposure. In addition, LPS stimulation notably upregulated the protein levels of citrullinated NEMO and nuclear NF-κB p65, which was restored by PAD4 knockdown. Furthermore, TNF-α treatment partially counteracted the effects of PAD4 knockdown on the secretion of IL-6, MCP-1 and IL-12, which are markers of inflammation, and invasion and migration in LPS-induced HTR8/SVneo cells. To conclude, these results suggest that PAD4 silencing can suppress inflammation whilst promoting invasion and migration by trophoblast cells through inhibiting the NEMO/NF-κB pathway. These findings furthered the understanding in the complex molecular mechanism that can trigger PE and provide a promising target for the treatment of this disease.

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“…However, the mechanism via which draM1 induces apoptosis or autophagic apoptosis remains unclear. in addition, it has been reported that inflammation-associated apoptosis is regulated by Bcl-2 and Bax (63,64), and that decreased invasion and migration ability of trophoblast cells induced by cell apoptosis in the placenta may be the major causes of PE (65,66). Therefore, the specific mechanism of DRAM1 and the relationship of between inflammation and Bcl-2 and Bax requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice

et al. 2020

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Preeclampsia (Pe) is a complication during pregnancy that is diagnosed by a new onset of hypertension and proteinuria. although the pathogenesis of Pe is not fully understood, a growing body of evidence indicates that oxidative stress and mitochondrial dysfunction might contribute to the progression of Pe. Therefore, the aim of the present study was to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in Pe, and to evaluate the role of dna damage-regulated autophagy modulator 1 (draM1) in the development of Pe. First, a mouse model of Pe induced by hypoxia-inducible factor 1α was established, and high levels of oxidative stress, apoptosis and mitochondrial dysfunction were found in the placentas of Pe mice. additionally, the placentas of Pe mice exhibited decreased mitophagy and significantly decreased DRAM1 expression. To further explore the role of draM1 in mitophagy, draM1 was overexpressed in the placental tissues of Pe mice, and this overexpression effectively improved the symptoms of Pe mice and significantly reduced blood lipid and urine protein levels. draM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of Pe mice. in addition, the overexpression of draM1 improved mitochondrial fusion and fission, and enhanced mitophagy. altogether, these results indicated a key role for draM1 in mitophagy that contributed to the regulation of Pe. To the best of the authors' knowledge, the present study provided the first evidence of a role for draM1 in Pe, and offered novel insight into the pathophysiological mechanisms of Pe.

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Knockdown of JARID2 inhibits the viability and migration of placenta trophoblast cells in preeclampsia

Cited by 7 publications

References 26 publications

MicroRNA analysis of medium/large placenta extracellular vesicles in normal and preeclampsia pregnancies

MicroRNA analysis of medium/large placenta extracellular vesicles in normal and preeclampsia pregnancies

PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF‑κB pathway

Role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice

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