Background/aims: The liver has the capacity to regenerate after partial hepatectomy. In order to clarify the mechanism of liver regeneration, we observed the initial stage, especially the mechanism of gene expression during progress from G0 to S phase (0-24 h), and attempted to identify new genes controlling progress to the S phase.

Methods: We applied large-scale gene expression analysis with complementary DNA microarrays in mouse hepatectomy models to clarify the mechanism of liver regeneration after partial hepatectomy.

Results: As a result, 23 new immediate-early gene candidates such as interleukin-1 receptor associated kinase-1 and karyopherin alpha-1, which are involved in transportation within the nucleus, were discovered. Candidates for new genes concerned with the progress to the S phase were discovered: inhibitor of DNA binding 2 (ID2) and inhibitor of DNA binding 3 (ID3), both new liver regeneration factors that promoted progress to the S phase, and GADD45 gamma (growth arrest and DNA-damage-inducible protein) as a factor inhibiting that process.

Conclusions: The above results not only suggest the importance of NFkappaB in the initial stage of liver regeneration but also points to the orderly maintenance of the proliferation of the cells in liver regeneration.

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http://dx.doi.org/10.1016/j.jhep.2003.11.005DOI Listing

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