Identification of de novo STAT3 target gene in liver regeneration.
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.
Zhang
Hui-Qi
HQ
Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, and Japan Association for the Advancement of Medical Equipment, Tokyo, Japan.
Haga
Sanae
S
Fukai
Moto
M
Oikawa
Yuko
Y
Inoue
Hiroshi
H
Ogawa
Wataru
W
Kano
Arihiko
A
Maruyama
Atsushi
A
Fu
Xin-Yuan
XY
Todo
Satoru
S
Enosawa
Shin
S
Ozaki
Michitaka
M