biostudies-literatureNiu GMing Wai Lau Centre for Reparative MedicineÅke Wiberg StiftelseVetenskapsrådetSwedish National Infrastructure for ComputingStiftelsen Syskonen Svenssons Stiftelse för Medicinsk ForskningWelander and Finsens FoundationCancerfondenLEO FondetRagnar Söderbergs stiftelsee2416784https://www.ebi.ac.uk/biostudies/studies/S-EPMC12224929biostudies-literatureUnknown12(25)The discovery of an increasing number of translatable circular RNAs (circRNAs) raises the question of whether their coding and non-coding functions can coexist within the same cell. This study profiles the dynamic expression of circRNAs during human skin wound healing. CircGLIS3(2) is identified, a circRNA whose levels transiently rise in dermal fibroblasts of acute wounds and are abnormally overexpressed in keloids, a fibrotic skin condition. Injury signals such as IL-1α, TGF-β, hypoxia, and ER stress induce both expression and cap-independent translation of CircGLIS3(2). The RNA form of CircGLIS3(2) activates fibroblasts into matrix-secreting cells, while its encoded protein promotes cell proliferation, collectively enhancing wound repair. Mechanistically, CircGLIS3(2) RNA stabilizes theAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair.PMC122249292020‐01400M31/15No. 20 0930 Pj23 2832 Pj2020-01400Toma MAWang ALi DSchlesinger DVegvari AXiao YPiipponen MOasa SElsasser SJVij MZhang LLiu ZXu Landen NWang QLuo LVukojevic VBian XChen YGeara JNiu GSommar PfalseCollaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair.The discovery of an increasing number of translatable circular RNAs (circRNAs) raises the question of whether their coding and non-coding functions can coexist within the same cell. This study profiles the dynamic expression of circRNAs during human skin wound healing. CircGLIS3(2) is identified, a circRNA whose levels transiently rise in dermal fibroblasts of acute wounds and are abnormally overexpressed in keloids, a fibrotic skin condition. Injury signals such as IL-1α, TGF-β, hypoxia, and ER stress induce both expression and cap-independent translation of CircGLIS3(2). The RNA form of CircGLIS3(2) activates fibroblasts into matrix-secreting cells, while its encoded protein promotes cell proliferation, collectively enhancing wound repair. Mechanistically, CircGLIS3(2) RNA stabilizes the2025-01-01T00:00:00Z2025 Jul2026-06-02T08:53:33.296Z2026-04-16T03:12:38.765ZS-EPMC122249294027950710.1002/advs.202416784