title: NUR77 inhibits the expression of TIMP2 and increases the migration and invasion of HTR-8/SVneo cells induced by CYR61.
abstract: OBJECTIVE
  To investigate the function and mechanism of CYR61 on the migration and invasion of the trophoblast cell line, HTR-8/SVneo cells.
  
  
  METHODS
  The mRNA and protein levels of NUR77 in the placentas of normal and preeclampsia (PE) women were evaluated using real-time PCR and Western blot, respectively. Paraffin-embedded tissues were processed for localization of NUR77 protein in placental villus by immunohistochemistry. HTR-8/SVneo cells were cultured in the presence of CYR61, Ad-NUR77 or a small interfering RNA for NUR77 (Ad-sinur77). The expression of NUR77 in the HTR-8/SVneo cells was detected and the effects of CYR61 on the migration and invasion of HTR-8/SVneo cells were assessed in wound-healing and transwell experiments, respectively. Gelatin zymography was used to measure the MMP2 release in HTR-8/SVneo cells.
  
  
  RESULTS
  NUR77 is significantly decreased in the placenta of women with PE compared with the levels during a normal pregnancy. CYR61 can significantly increase the expression of NUR77 in HTR-8/SVneo cells. CYR61, as well as NUR77, can promote HTR-8/SVneo cells migration and invasion, which can be blocked by Ad-sinur77. Both CYR61 and Ad-nur77 reduced the mRNA expression of TIMP2 in HTR-8/SVneo cells.
  
  
  CONCLUSIONS
  CYR61 may promote HTR-8/SVneo cells migration and invasion through the upregulation of NUR77, leading to the increase of MMP2 release and the downregulation of TIMP2 expression.
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Yan
authors.forename: Z
authors.initials: Z
authors.lastname: Diao
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D055515:Cysteine-Rich Protein 61 / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010920:Placenta / Q000737:chemistry / Q000166:cytology; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2