Granulocyte colony-stimulating factor (G-CSF) upregulates β1 integrin and increases migration of human trophoblast Swan 71 cells via PI3K and MAPK activation

• Autores: Furmento, Verónica A.; Marino, Julieta; Blank, Viviana C.; Cayrol, María Florencia; Cremaschi, Graciela A.; Aguilar, Rubén C.; Roguin, Leonor P.
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Experimental Cell Research; 2016 Mar 15;342(2):125-34
• Materia: EMBRION HUMANO; BIOLOGIA; QUIMICA BIOLOGICA; PLACENTA
• Institución: Pontificia Universidad Católica Argentina

Fil: Furmento, Verónica A. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Marino, Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Blank, Viviana C. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aguilar, Ruben Claudio. Department of Biological Sciences. Purdue University; Estados Unidos
Fil: Roguin, Leonor P. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
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.