title: HOXA9 transcriptionally regulates the EPHB4 receptor to modulate trophoblast migration and invasion.
abstract: Functional placenta formation is crucially dependent on extravillous trophoblast migration and invasion. EPHB4 has been identified to play a negative but important role in regulating trophoblast biological function, whereas the upstream regulation mechanism remains unknown. As reported, there is a transcriptional stimulation of EPHB4 expression consequent to HOXA9 activation in endothelial cells (ECs). Therefore, this study is conducted to investigate the role of HOXA9 and its relationship with EPHB4 in trophoblast cells.
  
  
  
  Both mRNA and protein expression levels of HOXA9 and EPHB4 were measured in preeclamptic placenta (n = 15) and normal placenta (n = 15). Next, the expression and location of HOXA9 and EPHB4 in first-trimester villi were shown via immunohistochemistry. Trophoblast cell line HTR-8/SVneo was used to explore the effect of HOXA9 on EPHB4 expression and trophoblast bioactivity by gain- and loss-of function studies. In addition, chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to clarify the regulation mechanism of HOXA9 on EPHB4 expression in HTR-8/SVneo.
  
  
  
  HOXA9 and EPHB4 expression were increased in preeclamptic placenta compared with normal placenta. HOXA9 could promote EPHB4 expression and impaired HTR-8/SVneo cells migration and invasion. ChIP and luciferase assays revealed that HOXA9 could directly bind to EPHB4 promoter and promoted its transcription.
  
  
  
  HOXA9 transcriptionally regulated EPHB4 expression to modulate trophoblasts migration and invasion, which may suggest a contribution of HOXA9-EPHB4 in the poor placentation in the pathogenesis of preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Minglian
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: SunshineLeo@hust.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000502:physiology*; D002824:Chorionic Villi / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D010929:Placentation / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D036224:Receptor, EphB4 / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: D018398:Homeodomain Proteins; C097899:homeobox protein HOXA9; D036224:Receptor, EphB4
keywords: EPHB4; HOXA9; Preeclampsia; Transcriptional regulation; Trophoblast