title: Increased NFAT5 expression stimulates transcription of Hsp70 in preeclamptic placentas.
abstract: OBJECTIVE
  We investigated the expression of heat shock protein 70 (Hsp70), nuclear factor of activated T cells 5 (NFAT5), and hypoxia-induced factor-1α (HIF-1α) in the placentas of normal and preeclamptic pregnancies and in human placental hypoxia models in vitro to examine the regulatory mechanisms of placental Hsp70 expression.
  
  
  METHODS
  The expression levels of HIF-1α, NFAT5, and Hsp70 were examined in placental samples from 10 females with preeclampsia and 10 normotensive control patients and in human choriocarcinoma trophoblast cells treated with 1 mM CoCl2 by western blotting. Using models of placental hypoxia, pharmacological inhibition of HIF-1α with chetomin and shRNA knockdown and overexpression of NFAT5 were performed to investigate the roles of HIF-1α and NFAT5 in induction of Hsp70 by placental hypoxia.
  
  
  RESULTS
  The levels of HIF-1α, NFAT5, and Hsp70 expression were significantly higher in the preeclamptic compared to normal placentas. In the placental hypoxia models, the expression of HIF-1α, NFAT5, and Hsp70 were significantly higher after 3, 6, and 12 h of 1 mM CoCl2 treatment, respectively. Pharmacological inhibition of HIF-1α suppressed the induction of NFAT5 and Hsp70 at the protein level. shRNA knockdown of NFAT5 suppressed the induction of Hsp70 protein and overexpression of NFAT5 stimulated the induction of Hsp70 mRNA and protein in models of human placental hypoxia in vitro.
  
  
  CONCLUSIONS
  HIF-1α positively regulates the induction of NFAT5 and Hsp70 by placental hypoxia and NFAT5 stimulates transcription of Hsp70 in response to placental hypoxia in models of human placental hypoxia in vitro.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: T G
authors.initials: TG
authors.lastname: Kang
authors.affiliation: Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: M Y
authors.initials: MY
authors.lastname: Kang
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: J E
authors.initials: JE
authors.lastname: Park
authors.affiliation: Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: I A
authors.initials: IA
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Shin
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: W J
authors.initials: WJ
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: S A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea; Department of Anatomy, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: W S
authors.initials: WS
authors.lastname: Choi
authors.affiliation: School of Nano-Bioscience and Chemical Engineering, Ulsan National Institute and Science and Technology, Ulsan, South Korea.
authors.forename: H M
authors.initials: HM
authors.lastname: Kwon
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, JinJu, South Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, JinJu, South Korea. Electronic address: wypaik@gnu.ac.kr.
authors.forename: W Y
authors.initials: WY
authors.lastname: Paik
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism; D003035:Cobalt; D004220:Disulfides / Q000494:pharmacology; D005260:Female; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004220:Disulfides; D018840:HSP70 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D026121:Indole Alkaloids; C118125:NFAT5 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; C001598:chetomin; D003035:Cobalt; C018021:cobaltous chloride
keywords: HIF-1α; Hsp70; NFAT5; Preeclamptic placenta