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

ANA C. RACCA; MAGALI E. RIDANO; SOLEDAD A. CAMOLOTTO; SUSANA GENTI DE RAIMONDI; GRACIELA M PANZETTA DE DUTARI

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 placentais formed by continuous fusion of the underlying villous cytotrophoblasts, thus maintaining placental functionality. Defects in this process are associatedwith pathologies like pre-eclampsia and intrauterine growth restriction. Kru¨ppel-like factor 6 (KLF6) is a transcription factor highlyexpressed in human and murine placenta. However, KLF6 functions in trophoblast cells remain largely unexplored. The aim of this work wasto address the role of KLF6 during STB formation. KLF6 knockdownthrough small interferingRNAexperiments hindered cell-cell fusion revealedby immunofluorescence microscopy in human primary villous cytotrophoblast as well as in the human placental-derivedBeWo cell line. Furthermore,KLF6 silencing led to a decrease in the expression of the fusogenic protein Syncytin-1 and the cell cycle regulator p21Cip1/Waf1measured byquantitative RT-PCR and western blot assays. On the contrary, transcript levels of genes that encode for proteins involved in STB formation suchas Syncytin-1, Syncytin-2, Connexin-43 and Zonula Occludens-1 increased when KLF6 was overexpressed in differentiating villous cytotrophoblastsand in non-fusing placental-derived JEG-3 cells. Interestingly, the expression of two trophoblast biochemical differentiation markers, bhCG andPSG3, were not reduced after KLF6 silencing in differentiating trophoblast cells. Present results support the notion that KLF6 is a relevant participantin cytotrophoblast fusion.