Hypoxia increases the expression of Kruppel like factor (KLF6) in the placenta

RACCA ANA; RIDANO MAGALI; BEVILACQUA ESTELA; GENTI DE RAIMONDI SUSANA; GRAHAM CH; PANZETTA DE DUTARI GRACIELA

Rosario

Congreso; L Reunión Anual de la SAIB; 2014

Preeclampsia (PE) is a pregnancy-specific disorder related to abnormal placental blood perfusion and poor trophoblast invasion. It is an important cause of maternal and fetal mortality and morbidity. While its pathophysiology 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-1α mediates low oxygen tension effects. KLF6 is a transcription factor highly expressed in placenta, involved incarcinogenesis and cell differentiation in various systems. Interestingly, in mouse kidney KLF6 expression is up-regulated following ischemia/reperfusion. Our aim was to elucidate whether placental KLF6 expression depends on oxygen 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 in PE placentas compared to control. According to these data, KLF6 is a potential mediator of hypoxic effects participating in normal and/or pathological placental development. Supported by CONICET, FONCyT, SECyT-UNC, and IUBMB and JCS fellowships.