KRUPPEL-LIKE FACTOR 6 IS AN IMPORANT TRANSCRIPTIONAL REGULATOR OF TROPHOBLAST DIFFERENTIATION

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

Potrero de los Funes, San Luis

Congreso; SAIB; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

KLF6 is a ubiquitous zinc finger transcription factor involved in differentiation, cell cycle control and proliferation in several cell systems. Even though its highest expression has been detected in human and mice placenta, its function in trophoblast physiology is still unknown. During pregnancy, placental villous cytotrophoblast cells (CTB) proliferate and differentiate by fusion to form the syncytiotrophoblast layer characterized by a high metabolic and biosynthetic activity. In this work, we postulate KLF6 as an important transcription factor that regulates the expression of genes implicated in trophoblast differentiation. KLF6 expression raised within the first hours of in-vitro CTB syncytialization preceding cell fusion and expression of ßhCG and PSG genes, early markers of trophoblast differentiation. Over expression of KLF6 in trophoblast-like JEG-3 cells increased the mRNA and protein levels of ßhCG and PSG genes, as revealed by qRT-PCR and western blot assays. Most importantly, down-regulation of KLF6 expression by siRNA experiments before the beginning of in-vitro syncytialization resulted in lower mRNA expression of trophoblast differentiation marker genes and inhibition of the CTB fusion process. In sum, these results represent the first direct evidence to propose KLF6 as a regulator of trophoblast differentiation. Supported by CONICET, FONCyT, MinCyT of Córdoba and SECyT-UNC