Saliva Exosomes-Derived UBE2O Promotes Angiogenesis in Cutaneous Wounds by Targeting SMAD6

Abstract Background Enhancing angiogenesis is critical for accelerating wound healing. Application of different types of exosomes (Exos) to promote angiogenesis represents a novel strategy for enhanced wound repair. Saliva is known to accelerate wound healing, but the underlying mechanisms remain unclear. Results Our results have demonstrated that saliva-derived exosomes (saliva-Exos) induce HUVEC proliferation, migration, and angiogenesis in vitro, and promote cutaneous wound healing in vivo. Further experiments documented that Ubiquitin-conjugating enzyme E2O (UBE2O) is one of the main components of saliva-Exos, and activation of UBE2O has effects similar to those of saliva-Exos, both in vitro and in vivo. Mechanistically, UBE2O decreases the level of SMAD6, thereby activating BMP2, which, in turn, induces angiogenesis. Conclusions The present work suggests that administration of saliva-Exos and UBE2O represents a promising strategy for enhancing wound healing through promotion of angiogenesis.