Reprogramming of diabetic wounds by Sox2 triggers a pro-healing transcriptional signature

We show that a combinatorial upregulation of SOX2 and hyperglycemia in cutaneous keratinocytes triggers a pro-healing signature and increased neutrophil chemoattraction, putatively by Ccr2, Ccr5, and Csf3r signaling. Neutrophil depletion and deregulation through the TREM1/FOXM1 pathway are directly implicated in diabetic foot ulcer (DFU) pathophysiology. Our results highlight the role of neutrophil recruitment in wound healing and can be used to explore potential therapeutic targets for DFUs in patients. Whole skin mRNA profiles in unwounded transgenic skin from mice treated with an ethanol vehicle, tamoxifen, vehicle and streptozotocin, or tamoxifen and streptozotocin were examined in triplicate or quadruplicate.