LEPTIN PROMOTES TROPHOBLASTIC CELL INVASION INVOLVING BETA-CATENIN/WNT PATHWAY

TAMARA FERNANDEZ ARANGUREN; AYELEN TORO; JULIETA MAYMÓ; MALENA SCHANTON; BERNARDO MASKIN; RODRIGO RIEDEL; MARIANA JAIME; CECILIA VARONE

Mar del Plata, Buenos Aires, Argentina

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placentaltrophoblasts where it works as a paracrine and autocrine hormone. It has been shown thatduring pregnancy leptin modulates migration and invasion of trophoblastic cells. In recent studies it has been determined that leptin reduces the level of E-Cadherin and increases theexpression of β1-Integrin in Swan-71 cells. In the present work, we aimed to study the molecular mechanisms that mediate the effect ofleptin regulation of trophoblastic cells invasion in placenta.We use Swan-71 cells, a first trimester trophoblastic human cell line, cultured under standardconditions, as well as human term placenta explants. Swan-71 cells and placental explantswere treated with different concentrations (50, 100 and 250 ng/ml) of recombinant leptin during48 h (Swan-71cells) or 20 h(placenta explants). Metalloproteinases 2 and 9 (MMP-2 and MMP9) were assessed by qRT-PCR and zymography. β-Catenin expression was determinedby Western-Blot and immunofluorescence analysis. Invasion experiments using trans-wellscovered with Matrigel were also performed.We determined that leptin treatment increased invasion of trophoblastic cells. Leptin alsoenhanced MMP-2 and MMP-9 expression and activity. The effect of leptin on the expression of β-Catenin as a possible activated pathway mediating invasion was studied. We determined that leptin treatment increased significantly the level of β-Catenin in Swan-71 cells (p