Low oxygen tension induces Krüppel-Like Factor 6 expression in trophoblast cells

BANDEIRA C; RACCA ANA; GENTI DE RAIMONDI SUSANA; BEVILACQUA ESTELA; RIDANO; GRAHAM CH; AVVAD-PORTARI E; PANZETTA DE DUTARI GRACIELA

PLACENTA

W B SAUNDERS CO LTD

Lugar: Londres; Año: 2016 vol. 45 p. 50 - 57

0143-4004

The transcription factor Krüppel-Like Factor 6 (KLF6) has important roles in cell differentiation, angiogenesis,apoptosis, and proliferation. Furthermore, there is evidence that KLF6 is required for properplacental development. While oxygen is a critical mediator of trophoblast differentiation and function,the involvement of oxygen in the regulation of KLF6 expression remains unexplored. In the present studywe examined the expression of KLF6 in placental tissue from uncomplicated and preeclamptic pregnancies,the latter often characterized by an inadequately perfused placenta. We also determined theeffect of hypoxia and the involvement of Hypoxia-Inducible Factor 1a (HIF-1a) on the expression of KLF6in cultured trophoblast cells and placental tissues. Results revealed that villous, interstitial and endovascularextravillous cytotrophoblasts from placentas from normal and preeclamptic pregnancies expressKLF6. In addition, KLF6 immunoreactivity was higher in the placental bed of preeclamptic pregnanciesthan in those of uncomplicated pregnancies. We demonstrated that hypoxia induced an early andtransient increase in KLF6 protein levels in HTR8/SVneo extravillous cytotrophoblast cells and inplacental explants. Reoxygenation returned KLF6 protein to basal levels. Moreover, hypoxia-induced upregulationof KLF6 expression was dependent on HIF-1a as revealed by siRNA knockdown in HTR8/SVneocells. These results indicate that KLF6 may mediate some of the effects of hypoxia in placental development.The regulation of KLF6 protein levels by oxygen has significant implications for understandingits putative role in diseases affected by tissue hypoxia.