title: Transcription factors E2F1 and E2F3 are expressed in placenta but do not regulate MMP14.
abstract: BACKGROUND
  Preeclampsia is a serious complication of pregnancy for which there are no efficacious medical treatments. Soluble endoglin is as an anti-angiogenic factor that contributes to the pathogenesis of the disease, however little is known about its molecular regulation in placenta. Recent data has demonstrated E2F transcription factors directly regulate MMPs in metastatic disease. Of particular interest was the capacity of E2F1 and E2F3 to up-regulate MMP14, a protease that cleaves and releases soluble endoglin from placenta. The aim of this study was to characterize E2F1 and E2F3 in preeclamptic placenta and assess whether silencing affects soluble endoglin release.
  
  
  METHODS
  E2F1 and E2F3 mRNA, protein expression and localization were assessed in severe early onset preeclamptic and preterm control placentas (delivered <34 weeks gestation). E2F siRNA was administered to primary trophoblast and primary endothelial cells and effect on MMP14 mRNA expression and soluble endoglin secretion assessed.
  
  
  RESULTS
  E2F1 and E2F3 were localized to the syncytiotrophoblast. E2F1 was significantly down regulated in severe preeclamptic placentas, while E2F3 was unchanged. Silencing E2F1 did not decrease MMP14 expression in primary trophoblast or endothelial cells. However, E2F1 silencing resulted in a significant increase in soluble endoglin secretion from both cell types, and silencing of E2F3 also significantly increased soluble endoglin release from primary trophoblast.
  
  
  CONCLUSIONS
  This study demonstrates that E2F1 and E2F3 are present within the syncytiotrophoblast of placenta and that E2F1 is reduced in preeclampsia. Although silencing of either E2F1 or E2F3 does not alter MMP14 expression, both appear to regulate soluble endoglin release.
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia. Electronic address: t.klino@unimelb.edu.au.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kaitu'u-Lino
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Hastie
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Cannon
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: N J
authors.initials: NJ
authors.lastname: Hannan
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Tong
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000071063:Endoglin; D005260:Female; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D053511:Matrix Metalloproteinase 14
keywords: E2Fs; MMP14; Placenta; Preeclampsia; Soluble endoglin