Role of defensins in diabetic wound healing

Abstract

The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.

Keywords: Defensin; Diabetic wound; Inflammation; Re-epithelia-lization; Tissue regeneration; Wound healing.

Figure 1

Mechanism of refractory diabetic wounds. The mainstream views include: Hyperglycemic microenvironment, abnormal immune system and neuropathy. Hyperglycemic microenvironment results in the complex formation of advanced glycation end products (AGEs) and cytokines, as well as circulating progenitor cell dysfunction. AGEs can significantly inhibit the proliferation of endothelial cells and alter the structure of collagen and elastin in the vascular wall, causing microvascular injury in the wound. The hallmarks of abnormal immune system are polymorphonuclear cell dysfunction, late neutrophil infiltration and suppressed macrophage polarization. As a result, diabetic wound healing is delayed and susceptible to bacterial infections and even biofilm formation. Neuropathy is occasion of subcutaneous hemorrhage, ultimately leads to skin breakdown.

Figure 2

Role of defensins in diabetic wound healing. VEGF: Vascular endothelial growth factor; Ang: Angiogenin.