Keloid research: current status and future directions

Introduction: Keloids and hypertrophic scars are fibroproliferative disorders of the skin that result from abnormal healing of injured or irritated skin. Multiple studies suggest that genetic, systemic and local factors may contribute to the development and/or growth of keloids and hypertrophic scars. A key local factor may be mechanical stimuli. Here, we provide an up-to-date review of the studies on the roles that genetic variation, epigenetic modifications and mechanotransduction play in keloidogenesis. Methods: An English literature review was performed by searching the PubMed, Embase and Web of Science databases with the following keywords: genome-wide association study; epigenetics; non-coding RNA; microRNA; long non-coding RNA (lncRNA); DNA methylation; mechanobiology; and keloid. The searches targeted the time period between the date of database inception and July 2018. Results: Genetic studies identified several single-nucleotide polymorphisms and gene linkages that may contribute to keloid pathogenesis. Epigenetic modifications caused by non-coding RNAs (e.g. microRNAs and lncRNAs) and DNA methylation may also play important roles by inducing the persistent activation of keloidal fibroblasts. Mechanical forces and the ensuing cellular mechanotransduction may also influence the degree of scar formation, scar contracture and the formation/progression of keloids and hypertrophic scars. Conclusions: Recent research indicates that the formation/growth of keloids and hypertrophic scars associate clearly with genetic, epigenetic, systemic and local risk factors, particularly skin tension around scars. Further research into scar-related genetics, epigenetics and mechanobiology may reveal molecular, cellular or tissue-level targets that could lead to the development of more effective prophylactic and therapeutic strategies for wounds/scars in the future. Lay Summary Recent research indicates that the formation of keloids and hypertrophic scars clearly associates with genetic, epigenetic, systemic, and local risk factors, particularly skin tension around scars. These findings suggest that molecular, cellular, and/or tissue-level approaches that target one or more of these risk factors may be promising scar therapies. Further research into scar-related genetics, epigenetics, and mechanobiology is needed, as it is likely to help identify more effective prophylactic and clinical treatment strategies for wounds and scars.