(WHS-P69) MACROPHAGE-DERIVED EXTRACELLULAR VESICLES PROMOTE WOUND CLOSURE BY REGULATING KERATINOCYTE PROLIFERATION VIA MIR-425
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
Small extracellular vesicles (EVs) are released by cells and deliver biologically active payloads important in the intercellular signaling that coordinates the response of multiple cell types in cutaneous wound healing. Here we used a cutaneous injury in mice as a physiologically relevant donor of pro-reparative EVs to treat impaired wound healing. We established a functional screen for miRNAs that increased the pro-reparative activity of EVs and identified miR-425-5p as a mediator of keratinocyte proliferation. Based on the abundance of macrophages identified by transcriptomic profiling of the EV donor site, we tested transgenic mice expressing a tetraspanin CD9-GFP fusion protein under the control of a macrophage-specific promoter. These studies showed that a population of macrophage-derived EVs was internalized by dermal fibroblasts to regulate the proliferation of overlying keratinocytes that is mediated in part by miR-425-5p and supports a key role for EVs in mediating pro-reparative intercellular signaling.