• • ANGPTL4 knockout in EpSCs reduces cyclin E2/A2/B1 and Cdk1 expression while increasing Cdkn2a and Cdkn2b, leading to cell cycle arrest; this identifies ANGPTL4 as a critical regulator of EpSC proliferation, with potential for targeted therapies to enhance epidermal regeneration in chronic wounds.
• • PRL8a6 mediates ANGPTL4-induced EpSC proliferation by decreasing G1 phase population and increasing S and G2 phase populations, as shown by cell cycle analysis; this provides a specific molecular target for accelerating wound re-epithelialization, potentially reducing healing time in clinical settings.
• • Knockdown of either Angptl4 or Prl8a6 in periwound tissues impairs EpSC proliferation and delays wound healing in vivo, with Prl8a6 mRNA levels positively correlated with Angptl4 mRNA during healing; this validates the ANGPTL4-PRL8a6 axis as a therapeutic pathway for wound repair.
• • PRL8a6 is expressed in EpSCs and regulates proliferation under resting conditions and during wound re-epithelialization, representing the first report of its role in EpSCs; this opens new avenues for manipulating stem cell behavior in skin homeostasis and repair.