INVESTIGADORES
MARINO Veronica Julieta
congresos y reuniones científicas
Título:
MAPKs and PI3K/Akt pathways are involved in G-CSF-induced migration of a human trophoblast cell line
Autor/es:
FURMENTO VERÓNICA A.; VIVIANA C. BLANK; K. MADHIVANAN; C. AGUILAR; V. J. MARINO; L P ROGUIN
Lugar:
Mar del Plata
Reunión:
Simposio; Maternal-Fetal Interaction: From Fertilization to the Next Generation. VI SLIMP & V LASRI; 2015
Institución organizadora:
Latin American Society for Maternal Fetal Interaction and Placenta
Resumen:
MAPKs and PI3K/Akt pathways are involved in G-CSF-induced migration of a human trophoblast cell line Verónica A. Furmento1, Viviana C. Blank1, Kayalvizhi Madhivanan2, R. Claudio Aguilar2, V. Julieta Marino1, Leonor P. Roguin1. 1IQUIFIB (UBA-CONICET), Pharmacy and Biochemistry School, University of Buenos Aires, Argentina. 2University of Purdue, United States.The relevance of the hematopoietic cytokine Granulocyte-Colony Stimulating Factor (G-CSF) signaling and the biological function of G-CSF:G-CSF receptor interaction in placental tissue has been the focus of our lab for the last years. In this sense, we have previously reported that G-CSF upregulates MMP-2 and VEGF through PI3K/Akt and Erk1/2 activation in the human first trimester trophoblast Swan 71 cell line.Objectives: The aim of our work was to examine whether G-CSF modifies β1-integrin expression levels and actin cytoskeleton organization in Swan 71 cells. In addition, we studied the effect of G-CSF on cell migration as well as the signaling pathways involved in this process.    Methods: G-CSF effect on Swan 71 actin cytoskeleton was explored by immunocytochemistry after rodamin-phalloidin staining. β1-integrin expression levels following G-CSF stimulation were determined by Western blot assays. Cell migration was assessed by transwell chambers (Tr) and wound healing (Wh) assays. Pharmacological inhibitors and dominant negative mutants (DN) were used in Wh migration assays to inhibit MAPKs and PI3K/Akt pathways.Results: G-CSF induced actin cytoskeleton rearrangement (migratory phenotype) after 9 hr of stimulation (p<0.05). G-CSF also augmented 70-60% (p<0.01) β1-integrin expression levels after 4-8 h of incubation. G-CSF increased near 20% (p<0.05) cell migration after 9 hr (Tr) or 16 hr (Wh). Pre-incubation of cells with the specific inhibitors SB203580 (p38), PD98059 (MEK1) and Ly294002 (PI3K) diminished the increment in cell migration induced by G-CSF. Similar results were obtained after transfection of Swan 71 cells with DNs of p38, Erk1/2 and p85 PI3K subunit.Conclusions: We have shown for the first time that G-CSF promotes the acquisition of a migratory phenotype in Swan 71 cells. Both p38 and Erk1/2 MAPKs as well as PI3K/Akt appeared to be involved in G-CSF-induced migration. Our results support a G-CSF biological role during embryo implantation and placenta development.