Cyclophilin A inhibits trophoblast migration and invasion in vitro and vivo through p38/ERK/JNK pathways and causes features of preeclampsia in mice

Hu, Haoyue; Jiang, Jiaxin; Chen, Qian; Wei, Songren; Liu, Mian; Chen, Xia; Fan, Cui-Xia; Ma, Jing; Chen, Wenqian; Wang, Xuefei; Zhong, Ming

doi:10.1016/j.lfs.2020.118351

Cited by 8 publications

(10 citation statements)

References 42 publications

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“…TNFrelated apoptosis-inducing ligand (TRAIL) induced trophoblast cell invasion through downregulating miR-146a and upregulating CXCR4, EGFR and matrix metalloproteinase 2 (MMP2) [34]. Of note, inflammation, hypoxia and oxidative stress has been revealed to affect trophoblast invasion [36][37][38]. Dysregulated miR-146a expression was noticed in patients with recurrent pregnancy loss, concurrent with increased inflammatory and oxidative stress responses [39], and it could attenuate oxygen-glucose deprivation/reoxygenationinduced cardiomyocyte apoptosis [40].…”

Section: Discussionmentioning

confidence: 99%

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

et al. 2021

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Objective This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Methods Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Results Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. Conclusion miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

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Section: Discussionmentioning

confidence: 99%

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

et al. 2021

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“…The ERK1/2 phosphorylation levels and p-ERK/ERK ratio were noticeably reduced in the placental tissues of PE rats relative to the control group [ 35 ]. Cyclophilin A weakened the migratory and invasive abilities of trophoblast cells in vitro and in vivo and triggered PE-like features in pregnant mice by inactivating p38 MAPK and ERK1/2 signaling pathways [ 36 ]. Moreover, our previous study demonstrated that enforced expression of NR_002794 could induce cell apoptosis in SWAN71 cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of downstream targets and signaling pathways of long non-coding RNA NR_002794 in human trophoblast cells

Liang

et al. 2021

Bioengineered

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Preeclampsia (PE) is a huge threat to pregnant women. Our previous study demonstrated that long non-coding RNA (lncRNA) NR_002794 was highly expressed in placentas of PE patients and could regulate the phenotypes of trophoblast cells. However, the downstream regulatory mechanisms of NR_002794 remain unknown. In this text, some potential downstream targets or signaling pathways of NR_002794 were identified through RNA sequencing (RNA-seq) and bioinformatics analysis in SWAN71 trophoblast cells. Western blot assay demonstrated that NR_002794 inactivated protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways and activated cell apoptotic signaling in SWAN71 cells. Both RNA-seq and reverse transcriptionquantitative PCR (RT-qPCR) outcomes showed that NR_002794 up-regulation could notably inhibit the expression of C-C motif chemokine ligand 4 like 2 (CCL4L2), interleukin 15 receptor subunit alpha (IL15RA), interleukin 32 (IL32), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), while NR_002794 knockdown induced these gene expressions in SWAN71 cells. CCK-8, BrdU, Transwell, wound healing, and flow cytometry analyses showed that NR_002794 inhibited cell proliferation and migration and induced cell apoptosis through down-regulating TIE1 in SWAN71 cells. In conclusion, lncRNA NR_002794 could exert its functions by regulating AKT and ERK1/2 pathways and TIE1 expression in human trophoblast cells.

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“…The inclusion criteria and procedures for placental collection were in accordance with those described in our previous study. [ 58 ] In brief, the placentae were sliced with a sterile scalpel into three pieces of 1 cm 3 cubes near the umbilical cord within 30 min after delivery. After washed with phosphate‐buffered saline (PBS) for several times, the collected tissues were stored in a −80 °C refrigerator or fixed in 4% paraformaldehyde for later experiments.…”

Section: Methodsmentioning

confidence: 99%

Thrombospondin‐1 Regulates Trophoblast Necroptosis via NEDD4‐Mediated Ubiquitination of TAK1 in Preeclampsia

Hu,

Ma,

Peng

et al. 2024

Advanced Science

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Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin‐1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage‐associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin‐1 and GSK′872 restore the trophoblast survival while pan‐caspase inhibitor Z‐VAD‐FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B‐activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up‐regulates the expression of neuronal precursor cell‐expressed developmentally down‐regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48‐linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down‐regulation of THBS1 destabilizes TAK1 by activating NEDD4‐mediated, K48‐linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE.

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Cyclophilin A inhibits trophoblast migration and invasion in vitro and vivo through p38/ERK/JNK pathways and causes features of preeclampsia in mice

Cited by 8 publications

References 42 publications

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

Identification of downstream targets and signaling pathways of long non-coding RNA NR_002794 in human trophoblast cells

Thrombospondin‐1 Regulates Trophoblast Necroptosis via NEDD4‐Mediated Ubiquitination of TAK1 in Preeclampsia

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