title: Low oxygen tension induces Krüppel-Like Factor 6 expression in trophoblast cells.
abstract: 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 proper placental 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 study we 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 the effect of hypoxia and the involvement of Hypoxia-Inducible Factor 1α (HIF-1α) on the expression of KLF6 in cultured trophoblast cells and placental tissues. Results revealed that villous, interstitial and endovascular extravillous cytotrophoblasts from placentas from normal and preeclamptic pregnancies express KLF6. In addition, KLF6 immunoreactivity was higher in the placental bed of preeclamptic pregnancies than in those of uncomplicated pregnancies. We demonstrated that hypoxia induced an early and transient increase in KLF6 protein levels in HTR8/SVneo extravillous cytotrophoblast cells and in placental explants. Reoxygenation returned KLF6 protein to basal levels. Moreover, hypoxia-induced up-regulation of KLF6 expression was dependent on HIF-1α as revealed by siRNA knockdown in HTR8/SVneo cells. 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 understanding its putative role in diseases affected by tissue hypoxia.
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: A C
authors: AC
authors: Racca
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: M E
authors: ME
authors: Ridano
authors: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors: C L
authors: CL
authors: Bandeira
authors: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
authors: E
authors: E
authors: Bevilacqua
authors: Department of Pathology at Medical Sciences School, State University of Rio de Janeiro, Brazil.
authors: E
authors: E
authors: Avvad Portari
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: S
authors: S
authors: Genti-Raimondi
authors: Departments of Biomedical and Molecular Sciences and Urology, Queen's University, Kingston, Ontario, Canada.
authors: C H
authors: CH
authors: Graham
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: gpan@fcq.unc.edu.ar.
authors: G M
authors: GM
authors: Panzetta-Dutari
mesh_terms: D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D000075723:Kruppel-Like Factor 6 / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000075723:Kruppel-Like Factor 6
keywords: Hypoxia; Hypoxia inducible factor-1α; Krüppel-Like Factor 6; Placenta; Trophoblast