Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells

Gupta, Seema; Malhotra, Sudha Saryu; Malik, Ankita; Verma, Seema; Chaudhary, Piyush

doi:10.1111/aji.12436

Cited by 167 publications

(123 citation statements)

References 79 publications

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“…A variety of cytokines and growth factors such as interleukin-6 (IL-6), interleukin-11(IL-11), hepatocyte growth factor (HGF), leukemia inhibitory factor (LIF) and epidermal growth factor (EGF) are known to increase migration and invasion of trophoblast cells [7]. While factors like tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) are known to decrease the migration and invasion of trophoblast cells [8].…”

Section: Introductionmentioning

confidence: 99%

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Malik¹,

Pal²,

Gupta³

2017

PLoS ONE

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Invasion of trophoblast cells is spatio-temporally regulated by various cytokines and growth factors. In pregnancy, complications like preeclampsia, shallow invasion of trophoblast cells and low amounts of epidermal growth factor (EGF) have been reported. In the present study, regulatory mechanisms associated with EGF-mediated invasion in HTR-8/SVneo trophoblastic cells have been delineated. Treatment of HTR-8/SVneo cells with EGF (10 ng/ml) led to eight fold increase (p < 0.05) in invasion. Increased invasion of HTR-8/SVneo cells by EGF was associated with an increase in phosphorylation of ERK½. In addition, significant phosphorylation of STAT1 (ser 727) and STAT3 (both tyr 705 and ser 727 residues) was also observed, accompanied by a decrease in total STAT1. Inhibition of ERK½ phosphorylation by U0126 (10 μM) led to a significant decrease in EGF-mediated invasion with simultaneous decrease in the phosphorylated forms of STAT3 and STAT1. Decrease in total STAT1 was also reversed on inhibition of ERK½. Interestingly, inhibition of STAT3 by siRNA led to a significant decrease in EGF-mediated invasion of HTR-8/SVneo cells and phosphorylation of STAT1, but it did not have any effect on the activation of ERK½. On the other hand, inhibition of STAT1 by siRNA, also led to a significant decrease in the EGF-mediated invasion of HTR-8/SVneo cells, showed concomitant decrease in ERK½ phosphorylation and STAT3 phosphorylation at ser 727 residue. These results suggest cross-communication between ERK½ and JAK-STAT pathways during EGF-mediated increase in invasion of trophoblast cells; phosphorylation at ser 727 residue of both STAT3 and STAT1 appears to be critical.

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Section: Introductionmentioning

confidence: 99%

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Malik¹,

Pal²,

Gupta³

2017

PLoS ONE

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“…S15 shows the EGF pathway in humans with the median expression in FPKM of genes in the pathway shown. Notably, many of the genes on the GRB2MYC pathway are strongly expressed; their activation leads to an increase in migration and invasion in response to EGF binding to EGFR1 [38]. The Actin cytoskeleton pathway is depicted in Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The most significant genes which were associated with diffuse placenta shape include EREG (epiregulin), a ligand of EGFR, UNC93A (unc-93 homolog A ( C. elegans )), a gene similar to UNC93B1 (unc-93 homolog B1 ( C. elegans )) which is involved in the balancing between Tlr7 and Tlr9 immune response in mice [39], and WNT5A (Wnt family member 5A), which is a member of the Wnt ligand family whose signaling pathway has been implicated in motility in human trophoblast cells [38]. …”

Section: Resultsmentioning

confidence: 99%

The core transcriptome of mammalian placentas and the divergence of expression with placental shape

et al. 2017

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Introduction The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved. Method Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades. Results We identified a set of 115 core genes which is expressed (FPKM ≥ 10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed in Homo sapiens when compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, including EREG and WNT5A which are both associated with placental shape. Discussion 115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.

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“…In mammals, this pathway is involved in many biological processes such as immune regulation, stress responses, hormone signalling and development . During pregnancy, cAMP has been associated with decidualization of the endometrium, invasion of the trophoblast, syncytialization and placental function/physiology . Recently, cAMP was also implicated in ZIKV neuropathogenesis (Olmo et al ., 2017), which makes genes related to the cAMP pathway promising candidates for genetic association studies in the context of ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil

et al. 2018

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Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells

Cited by 167 publications

References 79 publications

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

The core transcriptome of mammalian placentas and the divergence of expression with placental shape

Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil

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