The role of keratinocyte function on the defected diabetic wound healing

Non-healing wounds are a major complication of diabetes that can lead to limb amputation and disability in patients. The normal process of wound repair progresses through well-defined stages including hemostasis, inflammation, proliferative, and remodeling, which may be impaired in diabetic wounds. In recent years, it has been reported that keratinocytes, a major cell type in human skin, play a key role in the healing process of wounds. In this overview, firstly, a summary of the wound healing process is provided and the role of keratinocytes in wound healing is briefly reviewed. Then, a set of evidence about the impaired keratinocytes activities in diabetic wounds and clinical trials focused mainly on improving keratinocytes in the context of diabetic wound therapeutics are summarized. Keratinocytes can produce signaling molecules that act in a paracrine and autocrine way, causing pleiotropic effects on various cell types. The affected cells respond to keratinocytes by creating several signaling molecules, which also adjust keratinocyte activation through wound healing. In diabetic wounds, disruption of various biological mechanisms leads to dysfunction of keratinocytes including impaired migration, adhesion, and proliferation. The function of abnormal keratinocytes can lead to poor diabetic wound healing. Taken together, clarification of molecular and functional disturbances of keratinocyte cells and applying them in diabetic wounds can contribute to enhanced treatment of diabetic wounds. Based on the location of keratinocytes in the epidermis and the central role of keratinocytes in the diabetic wound healing process, applying keratinocytes has great potential for the treatment of diabetic burn wounds.