Granulocyte colony-stimulating factor (G-CSF) upregulates beta1 integrin and increases migration of human trofoblast SWAN 71 cells via PI3K and MAPK activation

FURMENTO VERÓNICA; MARINO VEÓNICA J; BLANK VIVIANA C; CAYROL MARIA F; CREMASCHI GRACIELA A; AGUILAR CLAUDIO; ROGUIN LEONOR P

EXPERIMENTAL CELL RESEARCH

ELSEVIER INC

Lugar: Amsterdam ; Año: 2016 vol. 342 p. 125 - 134

0014-4827

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 metallo-proteinase-2 and the release of vascular endothelial growth factor in Swan71 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 pro-moted Swan71 cell migration. By using selective pharmacological inhibitors and dominant negative mutants we showed that PI3K, Erk1/2 and p38 pathways are required for promoting Swan71 cell motility. It was also demonstrated that PI3K behaved as an upstream regulator of Erk1/2 and p38MAPK. 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 Swan71 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.