Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds

Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and pro-liferation. Foxo1 deletion rescued the negative impact of diabetes on healing but had the opposite effect in nor-moglycemic mice. Diabetes in vivo and in high glucose conditions in vitro enhanced expression of chemokine (C-C motif) ligand 20 (CCL20) and interleukin-36g (IL-36g) in a Foxo1-dependent manner. High glucose–stimulated Foxo1 binding to CCL20 and IL-36g promoters an