Tissue Transglutaminase Impairs HTR-8/SVneo Trophoblast Cell Invasion via the PI3K/AKT Signaling Pathway

Cheng, Min; Liu, Zequn; Ji, Wanqing; Zheng, Jie; Zeng, Huiqian; Guo, Fang; He, Ping

doi:10.1159/000515086

Cited by 3 publications

(3 citation statements)

References 42 publications

(43 reference statements)

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“…These investigations have explored factors including inflammatory immune hyperactivation, lipid metabolism abnormalities, and inadequacies in uterine spiral artery remodeling. The diagnostic markers include the PI3K/AKT signaling pathway, [ 11 ] IL-15, [ 12 ] HMGB1-TLR4, [ 13 ] adiponectin, [ 14 ] uric acid, [ 15 ] and uterine artery flow doppler indices. [ 16 ] Both PE and FGR originate from placental factors, manifesting months before clinical diagnosis occurs.…”

Section: Discussionmentioning

confidence: 99%

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester

Xu,

Cheng,

Wang

2024

Medicine

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Background: To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. Methods: During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at −80 ℃. These samples were obtained from 105 pregnant women in a nested case–control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. Results: It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). Conclusion: Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.

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Section: Discussionmentioning

confidence: 99%

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester

Xu,

Cheng,

Wang

2024

Medicine

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“…Previous studies have suggested that the activated PI3K/AKT pathway in PE placentas is involved in trophoblast cell proliferation 21,22 . Besides, PI3K/AKT signaling is also involved in the regulatiion of trophoblast migration and invasion 23,24 . DR3 has been reported to be the upstream of PI3K 17 .…”

Section: Introductionmentioning

confidence: 99%

“… 21 , 22 Besides, PI3K/AKT signaling is also involved in the regulatiion of trophoblast migration and invasion. 23 , 24 DR3 has been reported to be the upstream of PI3K. 17 Therefore, we hypothesized that DR3 may affect the physiology of placental trophoblasts by regulating the PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

Death receptor 3 is involved in preeclampsia through regulating placental trophoblast cell physiology by inactivating the PI3K/AKT pathway

Yin,

Wang,

Zhang

et al. 2023

Immunity Inflam & Disease

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BackgroundPreeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated.ObjectiveOur research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms.MethodsHTR‐8/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR‐8/SVneo cells were analyzed via reverse transcription‐quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p‐PI3K, p‐AKT, PI3K, and AKT protein expression.ResultsUpregulation of DR3 obviously inhibited HTR‐8/SVneo cells viability, migration, and invasion, as well as promoted HTR‐8/SVneo cells apoptosis, as opposed to the control‐plasmid group. We also found that DR3‐plasmid enhanced cleaved‐caspase3 expression, reduced p‐PI3K and p‐AKT protein expression, and p‐PI3K/PI3K or p‐AKT/AKT ratio in HTR‐8/SVneo cells. Importantly, IGF‐1, a PI3K/AKT signaling pathway agonist, partially reversed the effects of DR3‐plasmid on the cell viability, migration, invasion, apoptosis, and PI3K/AKT signal pathway in HTR‐8/SVneo cells.ConclusionDR3 was involved in PE through regulating placental trophoblast cell physiology via PI3K/AKT pathway, which might be a promising therapeutic target for PE therapy.

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Exogenous Hydrogen Sulfide Prevents Necroptosis by Inhibiting p38MAPK Pathway Activation in JEG-3 Trophoblast Cells: A Role in Preeclampsia

Zhang,

Chen,

Shao

et al. 2024

Gynecol Obstet Invest

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Setting 7 subsection in abstract Objectives: Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high-glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study was aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE. Design: This is an in vitro experimental study. Participants: A total of 10 pregnant women with severe preeclampsia (PE) and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available. Methods: The expression and localization of necrotic proteins were assayed in human placenta samples and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor). Results: RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine-β-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS. Limitations: In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of preeclampsia. Conclusions: we proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1, and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H₂S protected cytotrophoblasts against CER-induced necroptosis via the p38MAPK pathway.

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Tissue Transglutaminase Impairs HTR-8/SVneo Trophoblast Cell Invasion via the PI3K/AKT Signaling Pathway

Cited by 3 publications

References 42 publications

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester

Death receptor 3 is involved in preeclampsia through regulating placental trophoblast cell physiology by inactivating the PI3K/AKT pathway

Exogenous Hydrogen Sulfide Prevents Necroptosis by Inhibiting p38MAPK Pathway Activation in JEG-3 Trophoblast Cells: A Role in Preeclampsia

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