title: Granulocyte colony-stimulating factor (G-CSF) upregulates β1 integrin and increases migration of human trophoblast Swan 71 cells via PI3K and MAPK activation.
abstract: Multiple cytokines and growth factors expressed at the fetal-maternal interface are involved in the regulation of trophoblast functions and placental growth, but the role of G-CSF has not been completely established. Based on our previous study showing that G-CSF increases the activity of matrix metalloproteinase-2 and the release of vascular endothelial growth factor in Swan 71 human trophoblast cells, in this work we explore the possible contribution of G-CSF to cell migration and the G-CSF-triggered signaling pathway. We found that G-CSF induced morphological changes on actin cytoskeleton consistent with a migratory cell phenotype. G-CSF also up-regulated the expression levels of β1 integrin and promoted Swan 71 cell migration. By using selective pharmacological inhibitors and dominant negative mutants we showed that PI3K, Erk 1/2 and p38 pathways are required for promoting Swan 71 cell motility. It was also demonstrated that PI3K behaved as an upstream regulator of Erk 1/2 and p38 MAPK. In addition, the increase of β1 integrin expression was dependent on PI3K activation. In conclusion, our results indicate that G-CSF stimulates β1 integrin expression and Swan 71 cell migration by activating PI3K and MAPK signaling pathways, suggesting that G-CSF should be considered as an additional regulatory factor that contributes to a successful embryo implantation and to the placenta development.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Furmento
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Marino
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Viviana C
authors.initials: VC
authors.lastname: Blank
authors.affiliation: Instituto de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), CONICET, Alicia M. de Justo 1600, Buenos Aires, Argentina.
authors.forename: María Florencia
authors.initials: MF
authors.lastname: Cayrol
authors.affiliation: Instituto de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), CONICET, Alicia M. de Justo 1600, Buenos Aires, Argentina.
authors.forename: Graciela A
authors.initials: GA
authors.lastname: Cremaschi
authors.affiliation: Department of Biological Sciences, Purdue University, 201 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Rubén C
authors.initials: RC
authors.lastname: Aguilar
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina. Electronic address: rvroguin@qb.ffyb.uba.ar.
authors.forename: Leonor P
authors.initials: LP
authors.lastname: Roguin
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D046888:Tissue Array Analysis; D014327:Trophoblasts / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D019012:Integrin beta1; D016179:Granulocyte Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: G-CSF; MAPK; Migration; PI3K; Swan 71 cells; β1 Integrin