Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Abstract

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.