Targeting Egfr-Mediated Cell Proliferation and Lipid Metabolism Separation Effectively Accelerate Liver Regeneration

  • Cell Prolif. 2026 Apr 22:e70214. doi: 10.1111/cpr.70214.
Yuelei Hu  1 ,  Shifei Song  1 ,  Ruilin Wang  2 ,  Ni An  3 ,  Jinmei Diao  3 ,  Yuguo Chen  1 ,  Juan Liu  3  4 ,  Guoyue Lv  1  5
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China.
  • 2. Department of Cadre's Wards Ultrasound Diagnostics. Ultrasound Diagnostic Center, The First Hospital of Jilin University, Changchun, Jilin, China.
  • 3. Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, China.
  • 4. School of Future Medicine, Beijing University of Chinese Medicine, Beijing, China.
  • 5. China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, Changchun, China.
PMID: 42019507 DOI: 10.1111/cpr.70214
Abstract

Hepatocyte proliferation restores liver mass after partial hepatectomy (PHx), but the metabolic cost of this process remains unclear. Single-nucleus transcriptomics of mouse liver 48 h after 70% PHx revealed that EGFR-FOXM1 signalling drives mitotic entry while simultaneously suppressing PPARα-ACSL1-mediated lipid catabolism. Consequently, triglycerides and free fatty acids accumulate in regenerating tissue. Activating PPARα with the agonist Wy-14643 released this metabolic brake, accelerated hepatocyte proliferation via HIF1α-FOXM1, and improved post-PHx recovery. These data identify lipid-metabolic reprogramming as an EGFR-dependent collateral effect that can be pharmacologically reversed to enhance liver regeneration in surgical patients, offering a readily translatable strategy to reduce post-operative liver failure and shorten hospital stay after major hepatectomy.

Keywords
Acsl1; Ppara; lipid metabolism; liver regeneration; metabolic reprogramming.
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