Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells

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dc.contributor.authorFrancis, Víctor Aen_ZA
dc.contributor.authorAbera, Aron Ben_ZA
dc.contributor.authorMatjila, Mushien_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.contributor.authorKatz, Arieh Aen_ZA
dc.date.accessioned2016-01-11T06:46:25Z
dc.date.available2016-01-11T06:46:25Z
dc.date.issued2014en_ZA
dc.description.abstractThe precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies. Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2 and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A.en_ZA
dc.identifier.apacitationFrancis, V. A., Abera, A. B., Matjila, M., Millar, R. P., & Katz, A. A. (2014). Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells. <i>PLoS One</i>, http://hdl.handle.net/11427/16224en_ZA
dc.identifier.chicagocitationFrancis, Víctor A, Aron B Abera, Mushi Matjila, Robert P Millar, and Arieh A Katz "Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16224en_ZA
dc.identifier.citationFrancis, V. A., Abera, A. B., Matjila, M., Millar, R. P., & Katz, A. A. (2013). Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells. PloS one, 9(6), e99680. doi:10.1371/journal.pone.0099680en_ZA
dc.identifier.ris TY - Journal Article AU - Francis, Víctor A AU - Abera, Aron B AU - Matjila, Mushi AU - Millar, Robert P AU - Katz, Arieh A AB - The precise regulation of extravillous trophoblast invasion of the uterine wall is a key process in successful pregnancies. Kisspeptin (KP) has been shown to inhibit cancer cell metastasis and placental trophoblast cell migration. In this study primary cultures of first trimester human trophoblast cells have been utilized in order to study the regulation of invasion and angiogenesis-related genes by KP. Trophoblast cells were isolated from first trimester placenta and their identity was confirmed by immunostaining for cytokeratin-7. Real-time quantitative RT-PCR demonstrated that primary trophoblast cells express higher levels of GPR54 (KP receptor) and KP mRNA than the trophoblast cell line HTR8Svneo. Furthermore, trophoblast cells also expressed higher GPR54 and KP protein levels. Treating primary trophoblast cells with KP induced ERK1/2 phosphorylation, while co-treating the cells with a KP antagonist almost completely blocked the activation of ERK1/2 and demonstrated that KP through its cognate GPR54 receptor can activate ERK1/2 in trophoblast cells. KP reduced the migratory capability of trophoblast cells in a scratch-migration assay. Real-time quantitative RT-PCR demonstrated that KP treatment reduced the expression of matrix metalloproteinase 1, 2, 3, 7, 9, 10, 14 and VEGF-A, and increased the expression of tissue inhibitors of metalloproteinases 1 and 3. These results suggest that KP can inhibit first trimester trophoblast cells invasion via inhibition of cell migration and down regulation of the metalloproteinase system and VEGF-A. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0099680 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells TI - Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells UR - http://hdl.handle.net/11427/16224 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16224
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0099680
dc.identifier.vancouvercitationFrancis VA, Abera AB, Matjila M, Millar RP, Katz AA. Kisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cells. PLoS One. 2014; http://hdl.handle.net/11427/16224.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentMRC/UCT Receptor Biology Research Groupen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Francis et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTrophoblastsen_ZA
dc.subject.otherPregnancyen_ZA
dc.subject.otherExtracellular matrixen_ZA
dc.subject.otherDAPI stainingen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherGene regulationen_ZA
dc.subject.otherMetalloproteasesen_ZA
dc.subject.otherCell migrationen_ZA
dc.titleKisspeptin regulation of genes involved in cell invasion and angiogenesis in first trimester human trophoblast cellsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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