Dedicator of Cytokinesis 5 Regulates Keratinocyte Function and Promotes Diabetic Wound Healing

Cutaneous wound healing is a fundamental biologic and coordinated process, failure to maintain this process contributes the dysfunction of tissue homeostasis, increasing global burden diabetic foot ulcerations. However, factors that mediate are not fully understood. Here, we identify pivotal role dedicator cytokinesis 5 (Dock5) in keratinocyte functions contributing skin healing. Specifically, Dock5 highly upregulated during proliferative phase repair predominantly expressed epidermal keratinocytes. It regulates adhesion, migration, proliferation influences extracellular matrix (ECM) deposition by facilitating ubiquitination transcription factor ZEB1 activate laminin-332/integrin signaling. Genetic ablation mice leads attenuated reepithelialization granulation formation, overexpression–improved can be abrogated LAMA3 knockdown. Importantly, expression edge reduced patients animal models diabetes, further suggesting direct correlation between its abundance capability. The rescue causes significant improvement reepithelialization, collagen deposition, ECM production, granulation. Our study provides potential therapeutic target for impairment diabetes.