Circular RNAs (circRNAs) are a novel class of RNA with combined 3’ and 5’ ends. An increasing number of circRNAs have been shown to play important biological roles; however, their expression and function in human skin wound healing remain largely elusive. We have profiled circRNA expression in human skin and wound tissues as well as in keratinocytes and fibroblasts isolated from these tissue samples. We found increased fibroblast expression of a circRNA derived from the GLIS3 gene (circGLIS3) in the wounds compared to the matched skin. Moreover, we showed that circGLIS3 promoted fibroblast activation and extracellular matrix production by enhancing TGF-β signaling. Accordingly, its silencing reduced wound contraction and re-epithelization of human ex vivo wounds. Mechanistically, we discovered that this circRNA bound to Procollagen C-endopeptidase enhancer 1 (PCPE-1) and enhanced the stability of this protein in the cytoplasm of dermal fibroblasts. Surprisingly, besides acting as a non-protein-coding RNA as most other circRNAs, circGLIS3 was also translated into a small protein peptide due to an active internal ribosome entry site (IRES) in its sequence, which was confirmed by mass spectrometry analysis and Western blotting. This circGLIS3-encoded peptide was mainly detected in the nucleus of fibroblasts, suggesting its potential role in regulating gene expression. Collectively, our study uncovers that circGLIS3 plays a vital role in dermal fibroblasts during wound repair. The insight gained from this project deepens our understanding of wound biology and may open a new avenue for circRNA-based therapeutics for hard-to-heal wounds.

ESDR596 - Elucidating the role of Circular RNA circGLIS3 in human skin wound healing

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.