Abstract

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, we identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA UpRegulated in Diabetic Skin), which regulates wound healing in diabetes mellitus. Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment in vitro and accelerated diabetic wound healing in vivo. Mechanistically, lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.