Keratinocyte Function in Normal and Diabetic Wounds and Modulation by FOXO1

Abstract

Diabetes has a significant and negative impact on wound healing, which involves complex interactions between multiple cell types. Keratinocytes play a crucial role in the healing process by rapidly covering dermal and mucosal wound surfaces to reestablish an epithelial barrier with the outside environment. Keratinocytes produce multiple factors to promote reepithelialization and produce factors that enhance connective tissue repair through the elaboration of mediators that stimulate angiogenesis and production of connective tissue matrix. Among the factors that keratinocytes produce to aid healing are transforming growth factor-β (TGF-β), vascular endothelial growth factor-A (VEGF-A), connective tissue growth factor (CTGF), and antioxidants. In a diabetic environment, this program is disrupted, and keratinocytes fail to produce growth factors and instead switch to a program that is detrimental to healing. Changes in keratinocyte behavior have been linked to high glucose and advanced glycation end products that alter the activities of the transcription factor, FOXO1. This review examines reepithelialization and factors produced by keratinocytes that upregulate connective tissue healing and angiogenesis and how they are altered by diabetes.

Microbiological effects in patients with leg ulcers and diabetic foot treated with Lucilia sericata larvae

“…An increased concentration of glucose and AGE decreases the proliferation of keratinocytes and their migrations, which impairs the healing process. 27 In our previous study, we assessed the influence of MDT on the healing process of wounds, and we noted that the used therapy gave expected results in the form of a decreased ulceration area. 28 Tantawi et al noted that there was a significant decrease in the number of bacteria as a result of larval therapy, before beginning they isolated 20 types of bacteria in a group of 14 patients, 29 whereas in our population of patients, we managed to isolate 23 different bacteria, of which most were aerobic bacteria.…”

Wound Healing Effect of Gintonin Involves Lysophosphatidic Acid Receptor/Vascular Endothelial Growth Factor Signaling Pathway in Keratinocytes

“…Proliferation and/or migration of keratinocytes are stimulated by activating phospholipase C (PLC)/Ca 2+ , extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT), and/or p38 mitogen-activated protein kinases (p38-MAPK) pathways [ 26 , 27 , 28 , 29 , 30 ]. On the other hand, in abnormal conditions, keratinocytes fail to produce appropriate growth factors and disrupt wound healing [ 31 ]. Therefore, controlling the biological events of these cell types may be important for promoting wound healing of the skin.…”

Microplasma Treatment versus Negative Pressure Therapy for Promoting Wound Healing in Diabetic Mice

“…Re-epithelialization plays a key role in wound closure [ 33 ]. To fully restore epidermal function at the wound site, epidermal regeneration is required through re-epithelialization, which involves keratinocyte proliferation, migration, and differentiation [ 34 , 35 , 36 ]. In the present study, both MP treatment and NPWT increased the re-epithelialization percentage (R) of the wound bed area from 29% to 26% for NP and 47% for the MP14 and MP28 groups.…”

“…Patients with diabetes have impaired re-epithelialization during wound healing [ 41 ]. Diabetic wounds have a microenvironment with elevated levels of glucose and ROS; high glucose levels reduce keratinocyte functions in vivo [ 36 ]. Diabetic wounds are also influenced by excess ROS production, which induces keratinocyte injury, dysfunction, and apoptosis [ 42 ] and enhances NO degradation [ 39 , 40 ].…”