KdPT: Novel protective role against impaired wound healing in diabetes?

Abstract

Diabetic ulcers are a major and therapeutic challenging complication in diabetes. Not only increased morbidity of affected patients but also extremely high costs on health care systems make the development of new therapeutic strategies an urgent necessity. Our group works on the pluripotent protective effects of melanocortin peptides in various inflammatory models. In this work, the effects of high glucose on keratinocytes and the protective effects of KdPT, a melanocortin derivative, against glucotoxicity, were investigated. High glucose adversely affected various vital cell functions, e.g. proliferation, metabolic activity, viability and migration. No significant induction of apoptosis or autophagy was observed. Using atomic force microscopy studies we showed that high glucose profoundly changes the cells’ biomechanical properties (diameter, elasticity). Induction of intracellular oxidative stress and endoplasmic reticulum stress mediated glucotoxicity. KdPT, a truncated tripeptide of alpha-MSH, significantly attenuated high glucose induced oxidative stress and antagonised the toxic effects of glucose on cell viability, metabolic activity and migration. Finally, using an ex vivo model of skin organ cultures we validated our in vitro generated data in a more physiological environment. In summary, our work creates a basis for better understanding the mechanisms of impaired wound healing in diabetes and possibly points towards novel therapies for diabetic ulcers.