Keap1 modulates the redox cycle and hepatocyte cell cycle in regenerating liver

Keap1 knockdown in mice resulted in a delay in S-phase entry and disruption of the cell cycle during liver regeneration.

• Keap1 negatively controls the activity of the Nrf2 transcription factor, which is important for managing oxidative stress.
• Following partial hepatectomy, Keap1 knockdown led to a loss of mitotic rhythm in replicating hepatocytes.
• Disruption of S-phase progression in Keap1 knockdown mice is linked to the dysregulation of several key proteins, including c-Met, EGFR, Akt1, p70S6K, Cyclin A2, and Cyclin B1.
• Normal regenerating livers showed redox fluctuations associated with hepatocyte cell cycle progression, while Nrf2 remained inactive.
• Severe disruption of both the redox cycle and the cell cycle in hepatocytes was observed with Keap1 knockdown.

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