Unlabelled: 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.
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http://dx.doi.org/10.1111/j.1872-034X.2007.00278.x | DOI Listing |
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