Signal Transduction in Trophoblast Invasion

Fitzgerald, Justine S.; Busch, Susann; Wengenmayer, Tobias; Foerster, Katharina; Motte, Torben de la; Poehlmann, Tobias G.; Markert, Udo R.

doi:10.1159/000087834

Cited by 60 publications

(55 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…33 This study has shown that reduced HLX expression in cultured trophoblast cells significantly alters genes in the MAPK pathway. Therefore, HLX may play an important role in directly signaling trophoblast function via the MAPK pathway, which consists of several tumor suppressor genes and cell cycle regulators.…”

Section: Discussionmentioning

confidence: 85%

“…[31][32][33] Of these, the two pathways that are frequently used by trophoblast cells are the Jak-Stat and MAPK pathways. 33 The human MAPK signaling pathway PCR array was used in this study.…”

Section: Hlx Inactivation Impairs Cd34mentioning

confidence: 99%

“…This commercially available PCR array encompassed the gene expression profiles of 84 genes related to the MAPK signaling pathway, which is an important signaling pathway in the regulation of human trophoblast function. 33 Members of the MAP kinase kinase kinase (MKKK), MAP kinase kinase (MKK), and MAPK families are represented on this array as well as transcription factors and genes whose expression is induced by MAPK signaling. In addition, the array also included genes related to scaffolding and anchoring.…”

Section: Pcr Arraymentioning

confidence: 99%

See 2 more Smart Citations

Downstream Targets of Homeobox Gene HLX Show Altered Expression in Human Idiopathic Fetal Growth Restriction

Rajaraman

Murthi

Pathirage

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Fetal growth restriction (FGR) , a clinically significant pregnancy disorder , is poorly understood at the molecular level. This study investigates idiopathic FGR associated with placental insufficiency. Previously, we showed that the homeobox gene HLX is expressed in placental trophoblast cells and that HLX expression is significantly decreased in human idiopathic FGR. Here , we used the novel approach of identifying downstream targets of HLX in cell culture to detect potentially important genes involved in idiopathic FGR. Downstream targets were revealed by decreasing HLX expression in cultured trophoblast cells with HLX-specific small interfering RNAs to model human idiopathic FGR and comparing these levels with controls using a real-time PCR-based gene profiling system. Changes in candidate HLX target mRNA levels were verified in an independent trophoblast cell line, and candidate target gene expression was assessed in human idiopathic FGR-affected placentae (n ‫؍‬ 25) compared with gestation-matched controls (n ‫؍‬ 25). The downstream targets RB1 and MYC , cell cycle regulatory genes , showed significantly increased mRNA levels in FGR-affected tissues compared with gestation-matched controls , whereas CCNB1 , ELK1 , JUN , and CDKN1 showed significantly decreased mRNA levels (n ‫؍‬ 25 , P < 0.001 , t-test). The changes for RB1 and CDKN1C were verified by Western blot analysis in FGR-affected placentae compared with gestation-matched controls (n ‫؍‬ 6). We conclude that cell cycle regulatory genes RB1 , MYC , CCNB1 , ELK1 , JUN , and CDKN1C , which control important trophoblast cell functions , are targets of HLX. (Am J

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Hlx Inactivation Impairs Cd34mentioning

confidence: 99%

Section: Pcr Arraymentioning

confidence: 99%

See 1 more Smart Citation

Downstream Targets of Homeobox Gene HLX Show Altered Expression in Human Idiopathic Fetal Growth Restriction

Rajaraman

Murthi

Pathirage

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…It has been involved in oocyte maturation and in the regulation of trophoblast invasion and placental development (Hatano et al 2003, Fitzgerald et al 2005. It has been reported that MAPK cascade can modulate PKA activation by different mechanisms (Gerits et al 2008).…”

Section: Signal Transduction Pathways Mediating Leptin Inductionmentioning

confidence: 99%

Involvement of leptin in the molecular physiology of the placenta

Schanton¹,

Maymó²,

Pérez-Pérez³

et al. 2018

Reproduction

View full text Add to dashboard Cite

Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli

show abstract

“…Multiple signalling pathways control crucial processes involved in CTB proliferation and differentiation (Fitzgerald et al 2005). One such pathway is the JAK-STAT pathway (Park et al 2012, Yu et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction

Borg¹,

Yong²,

Lappas³

et al. 2015

Reproduction

View full text Add to dashboard Cite

Abnormal trophoblast function is associated with fetal growth restriction (FGR). The JAK-STAT pathway is one of the principal signalling mechanisms by which cytokines and growth factors modulate cell proliferation, differentiation, cell migration and apoptosis. The expression of placental JAK-STAT genes in human idiopathic FGR is unknown. In this study, we propose the hypothesis that JAK-STAT pathway genes are differentially expressed in idiopathic FGR-affected pregnancies and contribute to abnormal feto-placental growth by modulating the expression of the amino acid transporter SNAT2, differentiation marker CGB/human chorionic gonadotrophin betasubunit (b-hCG) and apoptosis markers caspases 3 and 8, and TP53. Expression profiling of FGR-affected placentae revealed that mRNA levels of STAT3, STAT2 and STAT5B decreased by 69, 52 and 50%, respectively, compared with gestational-age-matched controls. Further validation by real-time PCR and immunoblotting confirmed significantly lower STAT3 mRNA and STAT3 protein (total and phosphorylated) levels in FGR placentae. STAT3 protein was localised to the syncytiotrophoblast (ST) in both FGR and control placentae. ST differentiation was modelled by in vitro differentiation of primary villous trophoblast cells from first-trimester and term placentae, and by treating choriocarcinoma-derived BeWo cells with forskolin in cell culture. Differentiation in these models was associated with increased STAT3 mRNA and protein levels. In BeWo cells treated with siRNA targeting STAT3, the mRNA and protein levels of CGB/b-hCG, caspases 3 and 8, and TP53 were significantly increased, while that of SNAT2 was significantly decreased compared with the negative control siRNA. In conclusion, we report that decreased STAT3 expression in placentae may contribute to abnormal trophoblast function in idiopathic FGR-affected pregnancies.

show abstract

Signal Transduction in Trophoblast Invasion

Cited by 60 publications

References 93 publications

Downstream Targets of Homeobox Gene HLX Show Altered Expression in Human Idiopathic Fetal Growth Restriction

Downstream Targets of Homeobox Gene HLX Show Altered Expression in Human Idiopathic Fetal Growth Restriction

Involvement of leptin in the molecular physiology of the placenta

Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction

Contact Info

Product

Resources

About