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Diploid Hepatocytes Resist Acetaminophen-Induced Liver Injury Through Suppressed JNK Signaling.


ABSTRACT:

Background & aims

The liver contains both diploid and polyploid hepatocytes, but their functional differences remain poorly understood. Emerging evidence suggests that each ploidy state contributes to regeneration in an injury-specific manner. We hypothesized that diploid hepatocytes promote healing after acetaminophen (APAP)-induced liver injury.

Approach & results

To study ploidy populations in vivo, we utilized mice with a lifelong liver-specific knockout of E2f7/E2f8 (LKO), which are enriched in diploid hepatocytes (>70%) but otherwise normal. Control and LKO mice were treated with APAP (300 or 600 mg/kg), and injury was assessed over 0-96 hours. Although both groups sustained injury, LKO mice showed improved survival, lower serum liver enzyme levels

SUBMITTER: Wilson SR 

PROVIDER: S-EPMC12324546 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature