The molecular biology of chronic wounds and delayed healing in diabetes

Abstract

Wound healing is a complicated and integrated process. Although there is some tolerance in terms of redundancy and interrelated control mechanisms, pushing beyond such limits may contribute to delayed wound healing, and in extreme cases lead to chronic wounds/ulcers and thus potentially to lower extremity amputation. Diabetes is associated with such disruption in wound healing. Research in humans and in animal models has identified a large number of changes associated with diabetes at the molecular level in delayed wound healing and to a lesser extent in chronic diabetic ulcers. Better overall understanding of these changes and how they are interrelated would allow for specifically targeted treatment, thus ensuring improved quality of life for patients and providing savings to the high costs that are associated with all aspects of chronic diabetic ulcers. This review examines the work done at the molecular level on chronic diabetic ulcers, as well as considering changes seen in diabetes in general, both in humans and animal models, that may in turn contribute to ulcer formation.

High-Voltage Pulsed Current Stimulation Enhances Wound Healing in Diabetic Rats by Restoring the Expression of Collagen, <i>α</i>-Smooth Muscle Actin, and TGF-<i>β</i>1

“…A large number of molecular changes are associated with delayed wound healing in people with diabetic ulcers (Blakytny and Jude 2006). Our results show that the delayed wound healing observed in diabetic rat was associated with a significant increase of blood glucose levels.…”

“…About 1 week after wounding, fibroblasts stimulated by TGF-β differentiate into myofibroblasts, cells responsible for wound contraction (Todd et al 2001;Ugarte and Brandan 2006). In addition, TGF-β directly stimulates collagen synthesis and decreases extracellular matrix degradation by fibroblasts (Blakytny and Jude 2006). Collagen is critical for the strength and integrity of extracellular matrix and for epithelialization during the later stages of wound healing (Brancato and Albina 2011;Ebaid et al 2011).…”

Blockade of TSP1-Dependent TGF-β Activity Reduces Renal Injury and Proteinuria in a Murine Model of Diabetic Nephropathy

“…44 TGF-␤ signaling is known to be impaired in diabetic skin wounds, resulting in reduced macrophage chemoattraction, angiogenesis, and extracellular matrix deposition with accelerated reepithelialization. 68,69 Treatment of diabetic wounds with active TGF-␤ normalizes wound healing. 51,52,70 The role of TSP1-dependent TGF-␤ activation in diabetic wound healing is not known.…”

Acute Primary Actinomycosis Involving the Hard Palate of a Diabetic Patient

“…It is believed that the high concentration of glucose in the wound fluid of patients with diabetes is the main reason for the increased bacterial growth seen in these patients. 5,12,13 According to Hirsch et al, 5 nondiabetic patients can resist bacterial invasion much more efficiently, whereas diabetic patients are more likely to succumb to the bacterial challenge. In addition, it is well known, although not completely understood, that diabetes mellitus impairs wound healing.…”