A novel regulator of human villous trophoblast fusion: the Krüppel-Like Factor 6

RACCA ANA; RIDANO, MAGALÍ; CAMOLOTTO SOLEDAD; GENTI DE RAIMONDI SUSANA; PANZETTA DE DUTARI GRACIELA

MOLECULAR HUMAN REPRODUCTION.

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2015 vol. 21 p. 347 - 358

1360-9947

Cell-cell fusion is an essential event during life. Throughout human pregnancy, the syncytiotrophoblast (STB) layer of the placenta is formed by continuous fusion of the underlying villous cytotrophoblasts so maintaining placental functionality. Defects in this process are associated with pathologies like preeclampsia and intrauterine growth restriction. Krüppel-Like Factor 6 (KLF6) is a transcription factor highly expressed in human and murine placenta. However, KLF6 functions in trophoblast cells remain largely unexplored. The aim of this work was to address the role of KLF6 during STB formation. KLF6 knockdown through small interfering RNA experiments hindered cell-cell fusion revealed by immunofluorescence microscopy in human primary villous cytotrophoblast as well as in the human placental-derived BeWo cell line. Furthermore, KLF6 silencing led to a decrease in the expression of the fusogenic protein Syncytin-1 and the cell cycle regulator p21 Cip1/Waf1 measured by quantitative RT-PCR and western blot assays. On the contrary, transcript levels of genes that encode for proteins involved in STB formation such us Syncytin-1, Syncytin-2, Connexin-43, and Zonula Occludens-1 increased when KLF6 was overexpressed in differentiating villous cytotrophoblasts and in non-fusing placental-derived JEG-3 cells. Interestingly, the expression of two trophoblast biochemical differentiation markers, βhCG and PSG3, were not reduced after KLF6 silencing in differentiating trophoblast cells. Present results support the notion that KLF6 is a relevant participant in cytotrophoblast fusion