Preeclampsia is Associated With Reduced ISG15 Levels Impairing Extravillous Trophoblast Invasion

Ozmen, Asli; Guzeloglu‐Kayisli, Ozlem; Tabak, Selcuk; Guo, Xin; Semerci, Nihan; Nwabuobi, Chinedu; Larsen, Kellie; Wells, Ali; Uyar, Asli; Arlıer, Sefa; Wickramage, Ishani; Alhasan, Hasan; Totary-Jain, Hana; Schatz, Frederick; Odibo, Anthony O.; Lockwood, Charles J.; Kayisli, Umit A.

doi:10.3389/fcell.2022.898088

Cited by 15 publications

(7 citation statements)

References 72 publications

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“…Our transcriptome analysis also shows that interferon-related signaling pathways, including ISGylation, are upregulated in TUA medium relative to TA medium. Pertinently, reduction in levels of ISG15 that is required for ISGylation is associated with preeclampsia and knockdown of ISG15 expression impairs invasion of HTR8/SVneo cells in culture 26 . ISGylation has also been reported to modulate the stability of multiple proteins, including YAP, P63, and HIF1α, which play a critical role in trophoblast development 27 .…”

Section: Discussionmentioning

confidence: 99%

Derivation of human trophoblast stem cells from placentas at birth

Karakis,

Britt,

Jabeen

et al. 2024

Preprint

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Human trophoblast stem cells (hTSCs) have emerged as a powerful tool for modeling the placental cytotrophoblast (CTB) in vitro. hTSCs were originally derived from CTBs of the first trimester placenta or blastocyst-stage embryos in trophoblast stem cell medium (TSCM) that contains epidermal growth factor (EGF), the glycogen synthase kinase-beta (GSK3β) inhibitor CHIR99021, the transforming growth factor-beta (TGFβ) inhibitors A83-01 and SB431542, valproic acid (VPA), and the Rho-associated protein kinase (ROCK) inhibitor Y-27632. Here we show that hTSCs can be derived from CTBs isolated from the term placenta, using TSCM supplemented with a low concentration of mitochondrial pyruvate uptake inhibitor UK5099 and lipid-rich albumin (TUA medium). Notably, hTSCs could not be derived from term CTBs using TSCM alone, or in the absence of either UK5099 or lipid-rich albumin. Strikingly, hTSCs cultured in TUA medium for a few passages could be transitioned into TSCM and cultured thereafter in TSCM. hTSCs from term CTBs cultured in TUA medium as well as those transitioned into and cultured in TSCM thereafter could be differentiated to the extravillous trophoblast and syncytiotrophoblast lineages and exhibited high transcriptome similarity with hTSCs derived from first trimester CTBs. We anticipate that these results will enable facile derivation of hTSCs from normal and pathological placentas at birth with diverse genetic backgrounds and facilitate in vitro mechanistic studies in trophoblast biology.

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Section: Discussionmentioning

confidence: 99%

Derivation of human trophoblast stem cells from placentas at birth

Karakis,

Britt,

Jabeen

et al. 2024

Preprint

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“…As previously reported, FOXP3 [446], TIMP4 [447], OAS3 [448], SOCS1 [128], CD74 [129], PLK1 [449], TGFB1 [450], RAPGEF1 [451], SERPINH1 [452], ATF5 [66], GATA6 [133], IGF2BP1 [453], IRX3 [454], FOXC2 [455], SNHG17 [456], TAF1C [457], HHIP (hedgehog interacting protein) [458], POMC (proopiomelanocortin) [459], DOK5 [76], COL1A1 [460], POSTN (periostin) [461], SOD3 [462], ADAMTS13 [463], FABP5 [464], MAPK11 [465], KCTD15 [83], HSPG2 [466], MST1 [467], MGAT2 [468], LGR5 [469], SPINK1 [470], CYP19A1 [471], PLAC8 [90], CD36 [472], AQP5 [473], GIPR (gastric inhibitory polypeptide receptor) [474], ARG1 [475], SORL1 [476], CD4 [477], F11R [478], LEPR (leptin receptor) [479], CDH13 [480], AR (androgen receptor) [481], FOXO1 [102], MALT1 [482], PAM (peptidylglycine alpha-amidating monooxygenase) [483], B2M [484], TCF4 [485], CAV2 [486], HSBP1 [487], COLEC12 [488], ADRA2A [489], SLC38A4 [490], TM6SF2 [491], GLP2R [111], KLB (klotho beta) [492], NFAT5 [493], PON2 [494], ZMAT3 [495], DST (dystonin) [426], MGST3 [496], COQ2 [118], EPHX2 [497], C2 [181] and FAM3C [120] are altered expression in type 2 diabetes mellitus. Previous studies have shown that DRD4 [498], TIMP4 [499], SOCS1 [500], CD74 [501], TGFB1 [502], ACTG2 [503], ISG15 [504], HOXC8 [505], SNHG17 [506], IL1RL1 […”

Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Polycystic ovary syndrome (PCOS) is is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems and cancer. The specific mechanism of PCOS and its complications remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS and its complications. The next generation squancing (NGS) datset GSE199225 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed for research. The expression of the hub genes was validated using receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs in total, including 478 up regulated genes and 479 down regulated gene. GO and REACTOME illustrated that DEGs in PCOS were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling and aggregation. Finally, through analyzing the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN and TCF4 by the Cytoscape software. This study uses a series of bioinformatics technologies to obtain hug genes and key pathways related to PCOS and its complications. These analysis results provide us with novel ideas for finding biomarkers and treatment methods for PCOS and its complications.

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“…Since it has been proven that oxidative stress is a characteristic feature o preeclamptic pregnancies [26], we evaluated the effect of oxidative stress on HTRA expression in HTR8/SVneo and BeWo cell lines; two placental cell lines were used a models of extravillous [27][28][29] and villous cytotrophoblast [30][31][32], respectively Moreover, the BeWo cell line can be used as a syncytiotrophoblast model whe syncytialization is induced by forskolin [25]. As shown in Figure 2, HTRA1 expressio was significantly increased under oxidative stress in both BeWo and HTR8/SVneo cell (Figure 2A).…”

Section: Oxidative Stress Increased Htra1 Protein Expression In Bewo ...mentioning

confidence: 99%

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

Tossetta

Fantone

Giannubilo

et al. 2023

CIMB

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The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine–protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

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Preeclampsia is Associated With Reduced ISG15 Levels Impairing Extravillous Trophoblast Invasion

Cited by 15 publications

References 72 publications

Derivation of human trophoblast stem cells from placentas at birth

Derivation of human trophoblast stem cells from placentas at birth

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

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