HYPOXIA INCREASES THE EXPRESSION OF KRÜPPEL LIKE FACTOR 6 (KLF6) IN THE PLACENTA

RACCA AC; RIDANO ME; BEVILACQUA E; GENTI-RAIMONDI S; GRAHAM CH; PANZETTA-DUTARI GM

Rosario, Santa Fé

Congreso; L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2014

Preeclampsia (PE) is a pregnancy-specific disorder related to abnormal placental blood perfusion and poortrophoblast invasion. It is an important cause of maternal and fetal mortality and morbidity. While itspathophysiology has not been fully elucidated, placental oxidative stress injury appears as one important mechanism.In addition, normal early placentation occurs in a relatively hypoxic environment and throughout this period, HIF-1αmediates low oxygen tension effects. KLF6 is a transcription factor highly expressed in placenta, involved in carcinogenesis and cell differentiation in various systems. Interestingly, in mouse kidney KLF6 expression is upregulatedfollowing ischemia/reperfusion. Our aim was to elucidate whether placental KLF6 expression depends onoxygen level. We found that hypoxia increases KLF6 expression early and transiently in placental cells and tissue.KLF6 up-regulation was partially dependent on HIF-1α as revealed by siRNA knockdown and western-blot assays.Furthermore, immunohistochemical analysis showed a decrease in the nucleo/cytoplasmic KLF6 expression ratio inPE placentas compared to control. According to these data, KLF6 is a potential mediator of hypoxic effectsparticipating in normal and/or pathological placental development. Supported by CONICET, FONCyT, SECyTUNC,and IUBMB and JCS fellowships.