An Nrf2-NF-kB cross-talk controls hepatocyte proliferation in the normal and injured liver

The liver has remarkable regenerative and detoxification capacities, which require the Nrf2 and NF-kB transcription factors. Although their individual functions in hepatocytes are well characterized, knowledge about their cross-talk in the adult liver is limited. Therefore, we deleted the genes for Nrf2, the NF-kB subunit p65 or both genes in adult hepatocytes of mice using AAV8-Cre viruses. Loss of p65 or both genes caused spontaneous liver inflammation and necrosis, combined with a progressive increase in hepatocyte proliferation. Gene expression profiling identified individual and common target genes of both transcription factors, including genes involved in the control of cell proliferation.