title: Identification of de novo STAT3 target gene in liver regeneration.
abstract: The process of liver regeneration is regulated by complex mechanisms. Although signal transducer and activator of transcription-3 (STAT3), a transcription factor which targets mainly mitotic genes, definitely plays an important role in liver regeneration, the exact roles of STAT3 are not completely understood.
  
  
  OBJECTIVE
  In this report, we tried to search for a new target of STAT3 involved in liver regeneration in mice.
  
  
  METHODS
  We generated liver-specific STAT3 knockout (L-S3KO) mice and a STAT3 knockout cell line of mouse origin. Using chromatin immunoprecipitation, we screened 12 genes to which STAT3 binds after partial hepatectomy (PH). Of these genes, we analyzed the S3-IE3 clone that is located on chromosome-3 and possesses STAT3 binding sites in it.
  
  
  RESULTS
  We showed that STAT3 binds to a specific site on S3-IE3, and that interleukin-6 (IL-6) stimulates its transcriptional activity. The mRNA and protein levels of the net gene, which is located downstream of S3-IE3, were negatively regulated in the control cells, but not in the STAT3 knockout cells after IL-6 stimulation. Similarly in in vivo mouse PH, the mRNA and protein levels of net were also negatively regulated after PH, but not in L-S3KO mice.
  
  
  CONCLUSIONS
  The net gene is located downstream of a newly-recognized STAT3 binding site (S3-IE3) and negatively regulated after IL-6 stimulation and PH, although its role is still unclear.
authors.affiliation: Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, and Japan Association for the Advancement of Medical Equipment, Tokyo, Japan.
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Zhang
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Fu
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Shin
authors.initials: S
authors.lastname: Enosawa
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki