Identification of de novo STAT3 target gene in liver regeneration

Hui Qi Zhang, Sanae Haga, Moto Fukai, Yuko Oikawa, Hiroshi Inoue, Wataru Ogawa, Arihiko Kano, Atsushi Maruyama, Xin Yuan Fu, Satoru Todo, Shin Enosawa, Michitaka Ozaki

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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. Aim: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)374-384
Number of pages11
JournalHepatology Research
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

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  • Cite this

    Zhang, H. Q., Haga, S., Fukai, M., Oikawa, Y., Inoue, H., Ogawa, W., Kano, A., Maruyama, A., Fu, X. Y., Todo, S., Enosawa, S., & Ozaki, M. (2008). Identification of de novo STAT3 target gene in liver regeneration. Hepatology Research, 38(4), 374-384. https://doi.org/10.1111/j.1872-034X.2007.00278.x