• ANGPTL4 expression is upregulated in epidermal stem cells (EpSCs) by proinflammatory cytokines and growth factors during wound healing, promoting EpSC proliferation.
• ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated regulation of cell cycle proteins, including upregulation of cyclins and Cdk1 and downregulation of Cdkn2a.
• Knockdown of Angptl4 or Prl8a6 in periwound tissue impairs EpSC proliferation and delays wound re-epithelialization, highlighting their therapeutic potential.
• The study identifies a novel molecular mechanism linking microenvironmental factors to ANGPTL4 and PRL8a6 in accelerating skin wound repair.