Abstract
Wound healing is a process of cutaneous barrier reconstruction that occurs after skin injury and involves diverse cytokines and cell types. Similar to several deubiquitinating enzymes, ubiquitin-specific protease 15 (USP15) can remove ubiquitin chains from specific proteins to rescue them from degradation. However, the regulatory role of USP15 in wound healing remains unclear. We investigated the dynamic function of USP15 in wound healing. First, in USP15 knockout mice, we observed a significant delay in wound closure. In addition, inhibition of cell proliferation and migration was observed in USP15-silenced human dermal fibroblasts. Through RNA sequencing, it was revealed that the transforming growth factor-β (TGF-β) pathway was suppressed after USP15 knockdown. Furthermore, coimmunoprecipitation demonstrated that USP15 could interact with TGF-β receptor I and promote its deubiquitination, thereby maintaining TGF-β signaling pathway activity by enhancing TGF-β receptor I stability. These observations shed light on the function and mechanisms of USP15-mediated modulation of the TGF-β signaling pathway during wound healing, thus providing a novel potential target for the treatment of refractory wounds.